Phage procapsids and capsids.
Abstract
Viruses are infectious particles that exist in a huge variety of forms and infect practically all living systems: animals, plants, insects and bacteria. Viruses that infect and use bacterial resources are classified as bacteriophages (or phages) and represent the most abundant life form on Earth. A phage can be described as a specific type of nano-machine that is able to recognise its environment, find a host cell, start infection, self-assemble and safeguard its genome until the next cycle of replication is initiated. Remarkable results have been obtained by combining cryo-EM, X-ray analysis and bioinformatics in structural studies of these nano-machines. In this review we will describe results of structural studies of phages that uncover their organisation in different conformations, thus facilitating our understanding of the functional mechanisms in supramolecular assemblies and helping us understand the usage of phages in medical treatments. Currently, antibiotic resistance is an enormous challenge that we face. The tailed phages could be used in place of antibiotics due to their high specificity to host cells, but more knowledge of their organisation and function is required.
Keywords
- viruses
- bacteriophage
- structural organisation
- infectivity
- function
- structural methods
- electron microscopy
1. Introduction
All living systems have many diseases that are often caused by small organisms such as bacteria or infectious particles consisting of proteins, nucleic acids and sometimes lipids. These particles are called viruses, use the resources of living cells for their own propagation and can be transmitted from one organism to another. Each type of particle infects its own host cells, and they can survive outside living organisms in very harsh conditions. some of them continue to replicate with cells despite the host’s defence mechanisms and remain dormant (latent) in their host cell, e.g. herpesviruses which reactivate at a later date to produce further attacks of the disease if the host’s defence system weakens [1].
Bacteriophages (or phages) are viruses that infect and use bacterial resources for their own reproduction. They are characterised by a high specificity to bacteria at infection and are very common in all environments. Their number is directly related to the number of bacteria present. It is estimated that there are more than 1030 tailed phages in the biosphere [2]. Phages are common in soil and readily isolated from faeces and sewage, as well as being very abundant in freshwater and oceans with an estimate of more than 10 million virus-like particles in 1 mL of seawater [3, 4].
Why study the structure-function relationship of phages? Currently, there are substantial problems with diseases caused by bacteria, especially in hospitals. Many pathogenic bacteria exist such as
A powerful method to circumvent this resistance is the use of phages in the treatment of bacterial infections [9]. Most current studies of phage therapy have focussed on acute infections in animals [10]. In order to regulate the mechanisms of phage infection, we need to know not only the phage structure but also the phage-cell surface interaction mechanism and the process of switching the cell replication machinery for phage propagation. One important factor that has to be considered is how phages are reproduced. Phages have two ways of propagation: lytic and lysogenic [11]. In the first case, phages cause the compete lysis of a cell, where it breaks open and subsequently dies after phage replication. In the second type of replication, a phage integrates its genome into the host bacterium’s genome or forms a circular replicon in the bacterial cytoplasm. The bacterium then continues to live and reproduce normally, but the phage genome is transmitted to progeny cells at each subsequent cell division. Changes in cell conditions such as radiation or certain chemicals can release the phage genome, causing proliferation of new phages via the lytic cycle. Therefore, for medical treatments we need to use only lytic phages, so they will exist in an organism, while the pathogenic bacteria are around but only infect those bacteria that have the appropriate receptors in the outer membrane. This is an important factor that can be used to affect specific bacteria without harming those ones that are essential for the health of humans and animals [10]. In this review we will focus on tailed phages as they are abundant and well studied and could be beneficial to medicine [12]. We will describe the general organisation and structural features of their components revealed by current structural methods.
2. Phages and their classification
Virus classification is based on characteristics such as morphology, type of nucleic acid, replication mode, host organism and type of disease. The International Committee on Taxonomy of Viruses (ICTV) has produced an ordered system for classifying viruses (https://talk.ictvonline.org/taxonomy/). Phages are found in a variety of morphologies: filamentous phages, phages with a lipid-containing envelope and phages with lipids in the particle shell (Figure 1A). They have a genome, either DNA or RNA, which can be single or double stranded, and contain information on the proteins that constitute the particles, additional proteins that are responsible for switching cell molecular metabolism in favour of viruses and, therefore, the information on the self-assembly process. The genome can be one or multipartite and is located inside the phage capsid. Nearly 5500 bacterial viruses have been characterised by electron microscopy (EM) [15]. The shape of viruses is closely related to their genome, and a large genome indicates a large capsid and therefore a more complex organisation. The most studied group of phages is the tailed phages (order
3. Methods used for structural studies of viruses
The first ideas on how viruses infect cells were based on results obtained by microbiology and bacteriology during the last century. Understanding the function of viruses and how this can be regulated and modified requires knowledge of their structural organisation. However, investigation of structure-function relationships needs a combination of different techniques. Microbiology has identified viruses as infectious agents, while bacteriology and light microscopy enabled us to identify specificity between viruses and host cell interactions and to recognise a level of survival of bacteria in the presence of different phages. In order to understand interactions at the molecular level, one needs to know the structural features of the viruses and their components at an atomic level. Different structural techniques are often utilised for smaller components, and the results fitted into larger EM structures.
3.1 X-ray crystallography
X-ray crystallography was the first method used to study proteins at the atomic level, which is essential to reveal protein-ligand interactions that can boost or suppress protein activity. It is based on the principles of beam scattering within a crystal. By using specific software packages, a 3D electron density map of the protein that forms the crystal can be calculated [16]. However, to produce protein crystals, we need solutions of a protein at high concentration. The proteins have to be stable, and often mutations are made to remove their flexible parts, but this may produce different conformations to those that are required for their natural activity.
X-ray analysis is an efficient tool for analysis of protein complexes from a few kDa to hundreds of kDa in size. In order to study the structure of a large protein or a complex of several proteins, the process of crystallisation becomes a more challenging step. The development of cryoprotection in X-ray crystallography, where the crystals are flash frozen, has improved the quality of the data and often resulted in higher resolution. Nowadays, many structures of large protein complexes (up to 2–3 MDa) have been determined by X-ray analysis, but these projects have required decades to obtain high-quality crystals [17].
Viruses are much bigger particles and often have flexible components. The large size of the complexes results in significantly bigger unit cells, which results in technical challenges in obtaining fine structural details. Viruses with a rigid icosahedral lattice of the capsid have been studied successfully by X-ray crystallography at near-atomic resolution. The first viral structure was that of the
3.2 Nuclear magnetic resonance
Nuclear magnetic resonance (NMR) is an important technique that resolves structures of small proteins that are not suitable for crystallisation due to their flexibility. This method is based on exploiting the electrical charges and spins of the nuclei in a molecule. If an external magnetic field is applied, energy is transferred to the nuclei changing their state from the level of base energy to a higher energy. This energy is emitted when the spin returns back to its base level at a frequency corresponding to radio frequencies1. The signal that matches this transfer is measured and processed in order to yield a NMR spectrum [17, 20]. This technique is typically used for proteins of less than 200 amino acids and an upper weight limit of about 50 kDa, so it is unsuitable for the structural determination of complete viruses. However, it can be used to analyse flexibility of bigger complexes [21]. The NMR structures can be docked into low-resolution cryo-EM structures.
3.3 Electron microscopy
Light microscopy has been used for several centuries to study objects that are hardly visible to the naked eye. In conventional microscopy, resolution is mostly restricted according to the theoretical context of the Rayleigh criterion [22]. This limit is defined by the diffraction properties of light in lenses and has restricted our view to objects bigger than 250 nm. New developments in technology and advances in optical quality, electronics and software have delivered new options and extended the field of applications for electron microscopes allowing visualisation of single molecules. Electron microscopes use a beam of electrons (wavelength of less than 0.1 nm) instead of visible light
At the very beginning of EM evolvement, a method called negative staining was used for visualisation of biological complexes. In this case a drop of biocomplex solution is placed on a support grid and embedded in a heavy atom salt, usually uranyl acetate [24]. Since the specific density of the negative stain is much higher than the density of the biological molecules in the microscope, we can see the cast of the molecule merged into the surrounding stain. Where the stain did not penetrate into the molecule, one can see light spots in the image as the stain has blocked electrons. Sample preparation is fast and produces very high contrast. However, this technique does not allow fine details to be seen, and the particle becomes distorted due to the drying procedure required. The stain has a relatively large grain (up to 1.5 nm) that obscures details of the molecules under study.
Nearly four decades ago, a cryo-technique for sample preparation was introduced that allows biocomplexes to be kept at nearly native conditions. A thin layer of sample on a grid is flash frozen at liquid nitrogen temperatures, thus trapping molecules in a native, hydrated state within a thin layer of amorphous ice [25]. This technique is used to study the structural organisation of biocomplexes by cryo-electron microscopy (cryo-EM) or electron tomography (cryo-ET). Until two decades ago, all data in EM was collected on films that had to be developed and digitised, which was time-consuming. The advent of charge-coupled devices (CCDs) allowed direct digital acquisition of images and the collection of large numbers of particles giving rise to structures of higher resolution. Later, direct electron detectors were introduced into EM and are now used in all high-end electron microscopes [26]. Together with new approaches in microtechnology and the automation of data collection, the results from image analysis have improved tremendously. Cryo-EM is now approaching the near-atomic resolution that had only been achieved by X-ray crystallography. New maps obtained by cryo-EM provide information on the main polypeptide chains and often reveal the positions of side chains. The current highest resolution of structures currently deposited in the EMDB is 1.5 Å [27], with many others at a resolution between 3.5 and 4 Å. At this resolution atomic models can be built and refined using the crystallographic methods.
In cryo-ET the samples are also flash frozen, but data is collected by tilting the grid with the sample between −60 and 60° around the horizontal axis (perpendicular to the optical axis of the microscope) with an increment typically of 2°. The 2D images taken at each angle are combined to calculate a 3D map of the object. The limitation in the range of the tilt results in a cone of missing data [28]. The resolution in structures obtained by cryo-ET is lower than that in single-particle analysis. However, this approach allows visualisation of important organelles within cells. If there are multiple small structures such as ribosomes or viruses, then each structure can be extracted and averaged. This is called subtomogram averaging and will give higher-resolution structures [29].
4. Overall structural organisation of phages
Phages may have different shapes and sizes (Figure 1A). The most studied group is that of tailed phages with a dsDNA genome, and it also represents the largest group (Figure 1B). The tailed phages have three major components: a capsid where the genome is packed, a tail that serves as a pipe during infection to secure transfer of genome into host cell and a special adhesive system (adsorption apparatus) at the very end of the tail that will recognise the host cell and penetrate its wall. Cell resources are used for the phage reproduction.
The functional phage is a result of a multistep process that starts with all the necessary proteins produced by the host cell after infection: capsid, portal, tail, scaffolding, terminase, etc. (Figure 2). The capsids of the dsDNA phages often have fivefold or icosahedral symmetries [30], which are broken at one of the fivefold axes by the head-to-tail interface (HTI). The main component of the HTI is a dodecameric portal protein (PP) within the capsid. The PP represents the DNA-packaging motor, which is the crucial part of these nano-machines. The HTI also includes oligomeric rings of head completion proteins that play dual roles: (1) making an additional interface to molecules of ATP which provide energy for DNA packaging and (2) then connecting the portal protein and the tail. Some HTIs also serve as valves that close the exit channel preventing leakage of genome from the capsid but opening as soon as the phage is attached to the host cell. However, symmetries other than dodecameric have been found for nearly all PPs in vitro if the PPs are assembled under naive conditions, without any other phage protein components [31, 32, 33, 34, 35]. Typically, the main phage proteins have conservative folds despite low sequence similarity, although they may have different additional domains [36, 37].
The phage tail is the structural component of the phage that is essential during infection. Its adsorption apparatus located on the distal end of the tail recognises a receptor, or the envelope chemistry, of the host cell and ensures genome delivery to the cell cytoplasm. In
4.1 Procapsids
The capsid of a phage has a precursor formation, named the procapsid, during the assembly process (Figure 2). Scaffolding proteins (SPs) drive the assembly process by chaperoning major capsid protein (MCP) subunits to build an icosahedral procapsid that is later filled with dsDNA. The SPs are bound to the portal complex during formation of a procapsid with scaffolding inside. The sequence of conformational changes from a procapsid to the phage capsid where genome has been packed is named as the maturation process and goes through a series of intermediates [19, 38, 39, 40]. Some phages like HK97 and T5 do not have a separate SP; instead, the capsid protein is fused with a scaffolding domain at the N-terminus. As soon as the procapsid is assembled, the scaffolding domain is cleaved off and then like the separate SP will be removed from the capsid to make room for the genome [38, 39]. Structures of procapsids and mature virions have been determined for a number of phages (Table 1). The spherical capsid shell expands during maturation and becomes thinner due to alterations in the inter- and intra-subunit contacts.
Phage | Type of phage | Capsid protein | No. of residues | M. Mass (kDa) | Resolution (Å) | Structure analysis |
---|---|---|---|---|---|---|
HK97 | gp5 | 385 282 (AC) |
42 | 3.44 (C) 12 (PC) |
X-ray [42] EM [51] |
|
Т5 | pb8 | 458 299 (AC) |
51 | 9 (C) | EM [52] | |
λ | gpE | 341 | 38 | 6.8 (C),13.3 (PC) | EM [47] | |
SPP1 | gp13 | 324 | 35 | 8.8 (C) | EM [53] | |
TP901-1 | ORF36 | 272 | 29 | 15 | EM [54] | |
TW1 | gp57* | 352 | 39 | 7 | EM [55] | |
φ29 | gp8 | 448 | 50 | 8 | EM [56] | |
T7 | gp10 | 345 | 37 | 4.6 (PC) 3.6 (C) |
EM [57] | |
P22 | gp5 | 430 | 47 | 3.8 (PC) 4.0 (C) 3.3 (C) |
EM [58, 59, 60] | |
ε15 | gp7 | 335 | 37 | 4.5 | EM [50] | |
T4 | gp24 gp24* gp23 gp23* |
427 417 (AC) 521 456 (AC) |
47 44 56 49 |
2.9 (monomer) 3.3 (EM) |
X-ray [61] EM [62] | |
HSV-1 | VP5 | 1374 | 149 | 4.2 (C) | EM [63] |
4.2 Capsids
Most tailed phages have capsids of an icosahedral shape formed by multiple copies of one or more proteins. Icosahedral capsids are characterised by 12× fivefold, 20× threefold and 30× twofold axes, which give rise to 60 copies of the major independent parts [41]. A triangulation number (T number) describes the number of copies of the same protein within the independent part of the icosahedral lattice. The overall number of proteins in the virus corresponds to the T number multiplied by 60; for example, a T = 3 virus has 180 subunits [41]. Oligomers of the proteins that are located on the fivefold axes are referred to as pentons, while those complexes that are located on the faces of the icosahedron and form oligomers from six subunits are named as hexons.
Crystal structures were obtained for the Hoc protein from the T4-like phage RB49 with the capsid-binding C-terminal domain 4 missing [71] and Soc protein from the T4-like phage RB49 [72]. The Soc molecules, which are required for capsid stability, interact with three gp23* subunits [62] although not all binding sites were fully occupied possibly due to differences in the gp23* I-domain linkers. The immunogenic outer capsid Hoc protein was found in two different sites within the asymmetric unit: at the centre of the hexon near the icosahedral threefold axis and in the hexon close to the fivefold axis [62]. The density of Hoc near the threefold axis was less interpretable than that near the fivefold axis.
4.3 Connectors
In phages and herpesviruses, one of the fivefold vertices of the capsid is replaced by a
All currently known PPs are homo-dodecamers when extracted from the viral capsids, as that symmetry is imposed during self-assembly in vivo. However, naive assemblies in vitro of the PP complexes have some variations in their rotational symmetry with 13-mers being observed for SPP1, T7 and HK97 [31, 33, 74]. HSV has been shown to have 11-fold, 12-fold, 13-fold and sometimes even 14-fold symmetry [34]. While monomers of the different PPs vary in size, all of them share a common fold—shown by EM and X-ray structures that were obtained for the φ29, SPP1 and P22 portals [75, 76, 77, 78] and by cryo-EM for T7 and T4 (Table 2) [69, 79]. All known PP monomers are characterised by four domains: clip, stem, wing and crown (Figure 4) [77]. The clip domain is exposed to the capsid exterior and involved in binding to the terminase for DNA packaging [75, 80, 81] and later to a head completion protein during the HTI assembly [82]. The first high-resolution structure of a phage PP was obtained for the φ29 phage (Figure 4A, [75]). The clip domain is linked to the wing region through a stem that comprises typically two α-helices and the outer loops (Figure 4B,C). X-ray structures of PP from φ29 and SPP1 phages revealed major helical components that form the central channel through which DNA enters and exits the capsid. The structures of other PPs obtained later have confirmed that this is a conserved element characteristic for all known PPs. The wing domain radiates outwards from the central axis and has an α-helix, which is the longest one and serves as a spine of the wing. It has an α/β sub-fold at its periphery [77]. The crown domain consists of α-helices and is relatively small in SPP1 and surprisingly long (213 aa) in phage P22 (Figure 4B,D, Table 2).
Phage | PP | No. of residues | M. Mass (kDa) | Resolution (Å) | Structure analysis |
---|---|---|---|---|---|
HK97 | gp3 | 424 | 47 | none | |
T5 | pb7 | 403 | 45 | none | |
λ | gpB | 533 | 59 | none | |
SPP1 | gp6 | 503 | 57 | 3.4 (X-ray), ~7 (EM) | X-ray [77], EM [82] |
TP901-1 | ORF32 | 452 | 52 | 20 | EM [54] |
TW1 | gp24 | 459 | 51 | 21 | EM [55] |
φ29 | gp10 | 309 | 36 | 2.1 | X-ray [76] |
T7 | gp8 | 536 | 59 | 8, 12 | EM [87] |
P22 | gp1 | 725 | 83 | 10.5 (EM) 3.25 (X-ray) |
EM [88] X-ray [78] |
ε15 | gp4 | 556 | 61 | 20 | EM [89] |
T4 | gp20 | 524 | 61 | 3.6 | EM [69] |
HSV-1 | pUL6 | 676 | 74.2 | 8 | EM [90] |
4.4 Tails
The tail organisation in phages depends on their type:
Phage | Tail proteins | No. of residues | M. Mass kDa | Resolution (Å) | Structure analysis |
---|---|---|---|---|---|
HK97 | putative tail-component IPR010064, gp10 | not defined | not known | n/a | None |
Т5 | pb6 | 464 | 50 | 2.2 6 |
X-ray [97] EM [97] |
λ | gpV (TP) gpH (TMP) gpU (terminator) |
246 853 131 |
26 92 15 |
n/a 2.7 |
NMR [98, 102] X-ray [103] |
SPP1 | gp17 (TP) gp17* (TP) gp18 (TMP) |
134 264 1032 |
15 28 111 |
n/a 14 |
NMR (gp17) [104] EM [85] |
TW1 | gp12 (TP) gp14 (TMP) |
NF 675 |
18 72 |
23 | EM [55] |
φ29 | gp9 (knob) gp12 (tailspike) |
599 854 |
68 92 |
2.04 1.8–2.05 7.8 |
X-ray [105, 106] EM [56] |
T7 | gp11 (TP) gp12 (TP) gp17 (fibres) |
196 794 553 |
22 89 62 |
12.0 2.0 (X-ray) |
EM (gp11,12,17) [87] X-ray (gp17) [107] |
P22 | gp10 (hub) gp9 (tailspike) |
472 667 |
52 72 |
9.4 2.0 |
EM, tomography [88, 91], X-ray [108, 109] |
ε15 | gp20 (tailspike) | 1070 | 116 | 20n/r | EM [89, 110] |
T4 | gp19 (TP) gp15 (terminator) |
163 272 |
18 32 |
4.11 3.4 15.0 3.2 |
EM [111, 112] X-ray [113] |
HSV | does not have the tail | n/a | n/a | n/a | n/a |
4.5 Adsorption apparatus
Most
The structure of the T4 baseplate was assembled in vitro from gp10, gp7, gp8, gp6 and gp53, and the crystal structure was determined (4.2 Å) [141]. This indicated interesting differences compared to the structures when they are separately crystallised. However, about two-thirds of the structure was missing, but a cryo-EM structure of the same construct (3.8 Å) provided the positions of these missing parts [142]. The structures of T4 baseplate in its pre- and post-host attachment states were determined at 4.11 and 6.77 Å, respectively, by cryo-EM [111]. By combining high-resolution structures of the individual baseplate proteins, the authors were able to build a pseudo-atomic model for the baseplate proteins. The crystal structure at 2.9 Å of the gp5–gp27 cell-puncturing device was fitted into the EM structure (Figure 7F) [143]. Positions of gp27, gp5C (the C-terminal β-helix domain of gp5) and gp5* (the N-terminal OB-fold domain and the lysozyme middle domain) were identified. A monomeric protein gp5.4 caps the tip of the gp5 β-helix to sharpen the central spike [144]. During infection this spike punctures the cell membrane, and the lysozyme domain of gp5 digests the peptidoglycan in the
5. Conclusions
Structural studies of the currently known tailed phages have shown a common organisation, which implies that they have a single ancestor and diversity has arisen through evolution [37]. All phages have a similar pathway of self-assembly: a procapsid formed with the help of a SP (or sometimes a scaffolding domain); conformational changes induced by release of the SP create a space for the DNA, and assisted by DNA terminases, the genome is packaged into the procapsid. This step is typically named as the maturation of the capsid. The tail is then attached or assembled on the capsid to form the infectious virion. The MCPs are characterised by the HK97 capsid protein fold. However, phages have a very low sequence similarity, which leads to differences in how the capsid stability is arranged to withstand the high inner pressure of the genome. In some phages like HK97 and SPP1, the interactions between capsid proteins are strong and hold the capsid intact. In many phages the process of capsid maturation is linked to attachment of additional proteins that are named as auxiliary or decoration proteins. They are often essential to enhance the capsid stability. The HK97 capsid is held together by chain mail covalent links between the MCPs; in SPP1 and T5, the decoration proteins enhance stability of the capsid, but in λ, T4 and ε15 phages, these proteins are essential for keeping DNA inside the capsid [19, 52, 53].
The HTIs play an important role in all tailed phages as they provide a channel for DNA to enter and exit the capsid and at the same time provide a covalent connection to either the preassembled tails or tails assembled on the capsid. They all contain a dodecameric PP positioned within the capsid at one of the fivefold vertices and that acts as a gatekeeper holding the DNA within the capsid even in very harsh environments. Like the capsid proteins, the PPs have a common fold with the conserved elements being involved in interactions with DNA [145]. They have mostly α-helical domains in their central part and β-layers in the wing domains that interact with the capsid to fix the PP position. Head completion proteins below the PP also have similar folds to each other.
A much higher level of divergence is reflected in phage tail structures. The most common feature in all long-tailed phages is a central tube with a large number (30–40) of three- or sixfold circular rings of the major TPs. There is structural similarity between these major TPs: they have a similar fold of a β-sandwich flanked by alpha-helices and loops that provide links between adjacent rings. The helical tails have a typical rise of about 40 Å and rotation of around 20° between adjacent rings. Some tails also have appendages, which appear to have an immunoglobulin-like fold. Very little is known about the organisation of tail sheaths that have some similarities with type VI secretion systems, but sometimes they have extra appendages like immunoglobulin domains to help phages recognise their host cells. There is also some structural similarity of the TP with the tail terminator proteins and proteins in the T4 sheath.
Even higher diversity is found in the adsorption apparatus which are responsible for the recognition of the host cells and signalling the opening of the gate for the genome release. The tip of phage SPP1 recognises its receptor; induces the tail to be attached to the outer membrane of the host cell after disconnection of the tip. At the same time this interaction generates a signal that open the PP gate keeper. The T4 phage has a significantly more complex system of a baseplate which undergoes several steps of complex conformational changes.
Interestingly, the receptor-binding proteins also a have similar organisation: they are all trimers, usually intertwined with β-helical regions, and use their N-terminal domain to bind to the phage. Spikes and fibres are also found in many phages. However, the number of spikes or fibres varies significantly between phages. Podophages have trimeric tailspikes to recognise the specific host cell for infection. Like other phage components, they vary from six fibres in phage T7 to 12 in phage φ29, but they all have a β-helical fold. The fibres can have different roles within a phage, for instance, T4 has six long fibres that serve as host recognition and six short fibres which then extend and bind to the cell.
Antibiotics (especially of the broad-spectrum type) are very effective at killing infectious bacteria; however, they kill typically multiple bacterial species indiscriminately, thus destroying beneficial bacteria of the host microbiome as well. Since phages are specific to one species of bacteria, they are unlikely to perturb microbiome bacterial species. Current problems with antibiotic resistance require new approaches, and here phages can be used [12]. For medicinal purposes it is necessary to design a phage that will recognise the specific bacteria we want to eliminate [146]. Phages can be modified for high specificity in the recognition of pathogens. The high level of phage specificity is based on recognition of receptor characteristic for a given type of bacteria which is where the differences in the adsorption systems of different phages play a crucial role. The important task in studying phages is to find those that are able to kill only antibiotic-resistant bacteria. Here, the lytic phages are of most interest, since rather than stopping bacteria from producing a certain type of protein that will slow down the bacterium proliferation, like in the case of antibiotics, these phages destroy the bacteria’s cell wall and cell membrane completely. In addition, many bacteria develop biofilm—a thick layer of viscous materials that protect them from antibiotics. Some phages are equipped with tools that can digest this biofilm [147]. There are some problems with phages, since they are easy to use for topical applications, but often specific medications have to be administered internally. For phages to be used for delivery of drugs, they need to be more precise in their action. Consequently, we need to modify them so that the infectivity will be efficient by replacing the genome with DNA encoding specific enzymes and the adsorption apparatus made more effective. To develop these medical approaches, we need to know the phage organisation and the interactions between protein components at the atomic level. To achieve this hybrid, methods should be used including structural biology, biochemistry and microbiology [21].
Acknowledgments
The authors are grateful to Dr. D. Houldershaw and Mr. Y. Goudetsidis for their computer support. The authors apologise for the incomplete coverage of known phage structures and have drawn on a limited subset, owing to space constraints.
References
- 1.
Shors T. Understanding Viruses. Sudbury, USA: Jones and Bartlett Publishers; 2008. ISBN: 0-7637-2932-9 - 2.
Brussow H, Hendrix RW. Phage genomics: Small is beautiful. Cell. 2002; 108 :13-16 - 3.
Suttle CA. Marine viruses—Major players in the global ecosystem. Nature Reviews. Microbiology. 2007; 5 :801-812 - 4.
Breitbart M. Marine viruses: Truth or dare. Annual Review of Marine Science. 2012; 4 :425-448 - 5.
Coelho J, Woodford N, Turton J, Livermore DM. Multiresistant Acinetobacter in the UK: How big a threat? Journal of Hospital Infection. 2004;58 :167-169 - 6.
Hanlon GW. Bacteriophages: An appraisal of their role in the treatment of bacterial infections. International Journal of Antimicrobial Agents. 2007; 30 :118-128 - 7.
Burrowes B, Harper DR, Anderson J, McConville M, Enright MC. Bacteriophage therapy: Potential uses in the control of antibiotic-resistant pathogens. Expert Review of Anti-Infective Therapy. 2011; 9 :775-785 - 8.
Coates AR, Halls G, Hu Y. Novel classes of antibiotics or more of the same? British Journal of Pharmacology. 2011; 163 (1):184-194. DOI: 10.1111/j.1476-5381.2011.01250.x - 9.
Brussow H, Kutter E. Phage ecology. In: Kutter E, Sulakvelidze A, editors. Bacteriophages: Biology and applications. Boca Raton, FL: CRC Press; 2005. pp. 129-163 - 10.
Malik DJ, Sokolov IJ, Vinner GK, Mancuso F, Cinquerrui S, Vladisavljevic GT, et al. Formulation, stabilisation and encapsulation of bacteriophage for phage therapy. Advances in Colloid and Interface Science. 2017; 249 :100-133 - 11.
Weinbauer MG. Ecology of prokaryotic viruses. FEMS Microbiology Reviews. 2004; 28 :127-181 - 12.
Criscuolo E, Spadini S, Lamanna J, Ferro M, Burioni R. Bacteriophages and their immunological applications against infectious threats. Journal of Immunology Research. 2017; 2017 :3780697. Published online: Apr 6, 2017. DOI: 10.1155/2017/3780697 - 13.
Pietilä MK, Demina TA, Atanasova NS, Oksanen HM, Bamford DH. Archaeal viruses and bacteriophages: Comparisons and contrasts. Trends in Microbiology . 2014; 22 :6334-6344 - 14.
Orlova EV. Bacteriophages and Their Structural Organisation. In: Kurtböke İ, editor. Bacteriophages. IntechOpen; 2012. DOI: 10.5772/1065. ISBN: 978-953-51-0272-4 - 15.
Ackermann HW. Classification of bacteriophages. In: Calendar R, editor. The Bacteriophages. New York, USA: Oxford University Press; 2006. pp. 8-16. ISBN: 0-19-514850-9 - 16.
Drenth J. Principles of Protein X-Ray Crystallography. New York: Springer-Verlag; 2007 - 17.
Javed A, Christodoulou J, Cabrita LD, Orlova EV. The ribosome and its role in protein folding: Looking through a magnifying glass. Acta Crystallographica. Section D, Structural Biology. 2017; 73 (Pt 6):509-521. DOI: 10.1107/S2059798317007446 - 18.
Grimes JM, Burroughs JN, Gouet P, Diprose JM, Malby R, Ziéntara S, et al. The atomic structure of the bluetongue virus core. Nature. 1998; 395 :470-478 - 19.
Wikoff WR, Liljas L, Duda RL, Tsuruta H, Hendrix RW, Johnson JE. Topologically linked protein rings in the bacteriophage HK97 capsid. Science. 2000; 289 :2129-2133 - 20.
Cuniasse P, Tavares P, Orlova EV, Zinn-Justin S. Structures of biomolecular complexes by combination of NMR and cryoEM methods. Current Opinion in Structural Biology. 2017; 43 :104-113. DOI: 10.1016/j.sbi.2016.12.008 - 21.
Lengyel J, Hnath E, Storms M, Wohlfarth T. Towards an integrative structural biology approach: combining Cryo-TEM, X-ray crystallography, and NMR. Journal of Structural and Functional Genomics. 2014; 15 :117-124 - 22.
Ram S, Ward ES, Ober RJ. Beyond Rayleigh’s criterion: A resolution measure with application to single-molecule microscopy. Proceedings of the National Academy of Sciences of the United States of America. 2006; 103 (12):4457-4462 - 23.
Orlova EV, Saibil HR. Structural analysis of macromolecular assemblies by electron microscopy. Chemical Reviews. 2011; 111 (12):7710-7748. DOI: 10.1021/cr100353t - 24.
Harris JR. Negative Staining and Cryoelectron Microscopy, The Thin Film Techniques. Oxford, UK: BIOS Scientific Publishers; 1997. ISBN: 1859961207 - 25.
Adrian M, Dubochet J, Lepault J, McDowall AW. Cryo-electron microscopy of viruses. Nature. 1984; 308 (5954):32-36 - 26.
Ruskin RS, Yu Z, Grigorieff N. Quantitative characterization of electron detectors for transmission electron microscopy. Journal of Structural Biology. Journal of Structural Biology. 2013; 184 (3):385-393. DOI: 10.1016/j.jsb.2013.10.016. Published online: Nov 1, 2013, 10.1016/j.jsb.2013.10.016 - 27.
Bartesaghi A, Aguerrebere C, Falconieri V, Banerjee S, Earl LA, Zhu X, et al. Atomic resolution Cryo-EM structure of β-Galactosidase. Structure. 2018; 26 (6):848-856.e3. DOI: 10.1016/j.str.2018.04.004 - 28.
Wan W, Briggs JA. Cryo-electron tomography and subtomogram averaging. Methods in Enzymology. 2016; 579 :329-367. DOI: 10.1016/bs.mie.2016.04.014 - 29.
Briggs JAG. Structural biology in situ—The potential of subtomogram averaging. Current Opinion in Structural Biology. 2013; 23 :261-267 - 30.
Tavares P. The bacteriophage head-to-tail interface. Sub-Cellular Biochemistry. 2018; 88 :305-328. DOI: 10.1007/978-981-10-8456-0_14 - 31.
Orlova EV, Dube P, Beckmann E, Zemlin F, Lurz R, Trautner TA, et al. Structure of the 13-fold symmetric portal protein of bacteriophage SPP1. Nature Structural Biology. 1999; 6 :842-846 - 32.
Cingolani G, Moore SD, Prevelige PE Jr, Johnson JE. Preliminary crystallographic analysis of the bacteriophage P22 portal protein. Journal of Structural Biology. 2002; 139 :46-54 - 33.
Cerritelli ME, Trus BL, Smith CS, Cheng N, Conway JF, Steven AC. A second symmetry mismatch at the portal vertex of bacteriophage T7: 8-fold symmetry in the procapsid core. Journal of Molecular Biology. 2003; 327 :1-6 - 34.
Trus BL, Cheng N, Newcomb WW, Homa FL, Brown JC, Steven AC. Structure and polymorphism of the UL6 portal protein of herpes simplex virus type 1. Journal of Virology. 2004; 78 :12668-12671 - 35.
Lorenzen K, Olia AS, Uetrecht C, Cingolani G, Heck AJ. Determination of stoichiometry and conformational changes in the first step of the P22 tail assembly. Journal of Molecular Biology. 2008; 379 :385-396 - 36.
Hendrix RW, Smith MCM, Burns RN, Ford ME, Hatfull GF. Evolutionary relationships among diverse bacteriophages and prophages: All the world’s a phage. Proceedings of the National Academy of Sciences of the United States of America. 1999; 96 :2192-2197 - 37.
Bamford DH, Grimes JM, Stuart DI. What does structure tell us about virus evolution? Current Opinion in Structural Biology. 2005; 15 :655-663 - 38.
Wikoff WR, Conway JF, Tang J, Lee KK, Gan L, Cheng N, et al. Time-resolved molecular dynamics of bacteriophage HK97 capsid maturation interpreted by electron cryo-microscopy and X-ray crystallography. Journal of Structural Biology. 2006; 153 (3):300-306 - 39.
Huet A, Conway JF, Letellier L, Boulanger P. In vitro assembly of the T = 13 procapsid of bacteriophage T5 with its scaffolding domain. Journal of Virology. 2010; 84 :9350-9358. DOI: 10.1128/JVI.00942-10 - 40.
Veesler D, Quispe J, Grigorieff N, Potter CS, Carragher B, Johnson JE. Maturation in action: CryoEM study of a viral capsid caught during expansion. Structure. 2012; 20 :1384-1390 - 41.
Baker TS, Olson NH, Fuller SD. Adding the third dimension to virus life cycles: Three-dimensional reconstruction of icosahedral viruses from cryo-electron micrographs. Microbiology and Molecular Biology Reviews. 1999; 63 (4):862-922. (Review) - 42.
Helgstrand C, Wikoff WR, Duda RL, Hendrix RW, Johnson JE, Liljas L. The refined structure of a protein catenane: the HK97 bacteriophage capsid at 3.44 Å resolution. Journal of Molecular Biology. 2003; 334 :885-899 - 43.
Atanasova NS, Bamford DH, Oksanen HM. Haloarchaeal virus morphotypes. Biochimie. 2015; 118 :333-343 - 44.
Baker ML, Jiang W, Rixon FJ, Chiu W. Common ancestry of herpesviruses and tailed DNA bacteriophages. Journal of Virology. 2005; 79 :14967-14970 - 45.
Huet A, Makhov AM, Huffman JB, Vos M, Homa FL, Conway JF. Extensive subunit contacts underpin herpesvirus capsid stability and interior-to-exterior allostery. Nature Structural & Molecular Biology. 2016; 23 :531-539 - 46.
Yu X, Jih J, Jiang J, Hong Zhou Z. Atomic structure of the human cytomegalovirus capsid with its securing tegument layer of pp150. Science. 2017; 356 :1350 - 47.
Lander GC, Evilevitch A, Jeembaeva M, Potter CS, Carragher B, Johnson JE. Bacteriophage lambda stabilization by auxiliary protein gpD: Timing, location, and mechanism of attachment determined by cryoEM. Structure. 2008; 16 (9):1399-1406. DOI: 10.1016/j.str.2008.05.016 - 48.
Yang F, Forrer P, Dauter Z, Conway JF, Cheng N, Cerritelli ME, et al. Novel fold and capsid-binding properties of the lambda-phage display platform protein gpD. Nature Structural Biology. 2000; 7 (3):230-237 - 49.
Jiang W, Baker ML, Jakana J, Weigele PR, King J, Chiu W. Backbone structure of the infectious epsilon15 virus capsid revealed by electron cryomicroscopy. Nature. 2008; 451 (7182):1130-1134 - 50.
Baker ML, Hryc CF, Zhang Q , Wu W, Jakana J, Haase-Pettingell C, et al. Validated near-atomic resolution structure of bacteriophage epsilon15 derived from cryo-EM and modeling. Proceedings of the National Academy of Sciences of the United States of America. 2013; 110 :12301-12306 - 51.
Conway JF, Wikoff WR, Cheng N, Duda RL, Hendrix RW, Johnson JE, et al. Virus maturation involving large subunit rotations and local refolding. Science. 2001; 292 :744-748 - 52.
Vernhes E, Renouard M, Gilquin B, Cuniasse P, Durand D, England P, et al. High affinity anchoring of the decoration protein pb10 onto the bacteriophage T5 capsid. Scientific Reports. 2017; 7 :41662. DOI: 10.1038/srep41662 - 53.
White HE, Sherman MB, Brasilès S, Jacquet E, Seavers P, Tavares P, et al. Capsid structure and its stability at the late stages of bacteriophage SPP1 assembly. Journal of Virology. 2012; 12 :6768-6777. DOI: 10.1128/JVI.00412-12 - 54.
Bebeacua C, Lai L, Vegge CS, Brøndsted L, van Heel M, Veesler D, et al. Visualizing a complete Siphoviridae member by single-particle electron microscopy: The structure of lactococcal phage TP901-1. Journal of Virology. 2013; 87 (2):1061-1068. DOI: 10.1128/JVI.02836-12 - 55.
Wang Z, Hardies SC, Fokine A, Klose T, Jiang W, Cho BC, et al. Structure of the marine siphovirus TW1: Evolution of capsid-stabilizing proteins and tail spikes. Structure. 2018; 26 :238-248 - 56.
Tang J, Olson N, Jardine PJ, Grimes S, Anderson DL, Baker TS. DNA poised for release in bacteriophage phi29. Structure. 2008; 16 :935-943 - 57.
Guo F, Liu Z, Fang PA, Zhang Q , Wright ET, Wu W, et al. Capsid expansion mechanism of bacteriophage T7 revealed by multistate atomic models derived from cryo-EM reconstructions. Proceedings of the National Academy of Sciences of the United States of America. 2014; 111 (43):E4606-E4614. DOI: 10.1073/pnas.1407020111 - 58.
Parent KN, Khayat R, Tu LH, Suhanovsky MM, Cortines JR, Teschke CM, et al. P22 coat protein structures reveal a novel mechanism for capsid maturation: stability without auxiliary proteins or chemical crosslinks. Structure. 2010; 18 (3):390-401. DOI: 10.1016/j.str.2009.12.014 - 59.
Chen DH, Baker ML, Hryc CF, DiMaio F, Jakana J, Wu W, et al. Structural basis for scaffolding-mediated assembly and maturation of a dsDNA virus. Proceedings of the National Academy of Sciences of the United States of America. 2011; 108 (4):1355-1360 - 60.
Hryc CF, Chen DH, Afonine PV, Jakana J, Wang Z, Haase-Pettingell C, et al. Accurate model annotation of a near-atomic resolution cryo-EM map. Proceedings of the National Academy of Sciences of the United States of America. 2017; 114 :3103-3108 - 61.
Fokine A, Leiman PG, Shneider MM, Ahvazi B, Boeshans KM, Steven AC, et al. Structural and functional similarities between the capsid proteins of bacteriophages T4 and HK97 point to a common ancestry. Proceedings of the National Academy of Sciences of the United States of America. 2005; 102 (20):7163-7168 - 62.
Chen Z, Sun L, Zhang Z, Fokine A, Padilla-Sanchez V, Hanein D, et al. Cryo-EM structure of the bacteriophage T4 isometric head at 3.3-angstrom resolution and its relevance to the assembly of icosahedral viruses. Proceedings of the National Academy of Sciences of the United States of America. 2017; 114 :E8184-E8193 - 63.
Dai X, Zhou ZH. Structure of the herpes simplex virus 1 capsid with associated tegument protein complexes. Science. 2018; 360 (6384. pii: eaao7298). DOI: 10.1126/science.aao7298 - 64.
Holden HM, Ito M, Hartshorne DJ, Rayment I. X-ray structure determination of telokin, the C-terminal domain of myosin light chain kinase, at 2.8 Å resolution. Journal of Molecular Biology. 1992; 227 :840-851 - 65.
Xiang Y, Morais MC, Battisti AJ, Grimes S, Jardine PJ, Anderson DL, et al. Structural changes of bacteriophage φ29 upon DNA packaging and release. The EMBO Journal. 2006; 25 :5229-5239 - 66.
Morais MC, Choi KH, Koti JS, Chipman PR, Anderson DL, Rossmann MG. Conservation of the capsid structure in tailed dsDNA bacteriophages: The pseudoatomic structure of φ29. Molecular Cell. 2005; 18 :149-159 - 67.
Marchler-Bauer A, Anderson JB, Cherukuri PF, DeWeese-Scott C, Geer LY, Gwadz M, et al. CDD: A conserved domain database for protein classification. Nucleic Acids Research. 2005; 33 :D192-D196 - 68.
Iwasaki K, Trus BL, Wingfield PT, Cheng N, Campusano G, Rao VB, et al. Molecular architecture of bacteriophage T4 capsid: Vertex structure and bimodal binding of the stabilizing accessory protein, Soc. Journal of Virology. 2000; 271 :321-333 - 69.
Sun L, Zhang X, Gao S, Rao PA, Padilla-Sanchez V, Chen Z, et al. Cryo-EM structure of the bacteriophage T4 portal protein assembly at near-atomic resolution. Nature Communications. 2015; 6 :7548 - 70.
Fokine A, Chipman PR, Leiman PG, Mesyanzhinov VV, Rao VB, Rossmann MG. Molecular architecture of the prolate head of bacteriophage T4. Proceedings of the National Academy of Sciences of the United States of America. 2004; 101 :6003-6008 - 71.
Fokine A, Islam MZ, Zhang Z, Bowman VD, Rao VB, Rossmann MG. Structure of the three N-terminal immunoglobulin domains of the highly immunogenic outer capsid protein from a T4-like bacteriophage. Journal of Virology. 2011; 85 :8141-8148 - 72.
Qin L, Fokine A, O’Donnell E, Rao VB, Rossmann MG. Structure of the small outer capsid protein, Soc: A clamp for stabilizing capsids of T4-like phages. Journal of Molecular Biology. 2010; 395 (4):728-741. DOI: 10.1016/j.jmb.2009.10.007 - 73.
Heymann JB, Cheng N, Newcomb WW, Trus BL, Brown JC, Steven AC. Dynamics of herpes simplex virus capsid maturation visualized by time-lapse cryo-electron microscopy. Nature Structural Biology. May 2003; 10 (5):334-341 - 74.
Cardarelli L, Lam R, Tuite A, Baker LA, Sadowski PD, Radford DR, et al. The crystal structure of bacteriophage HK97 gp6: defining a large family of head-tail connector proteins. Journal of Molecular Biology. 2010; 395 :754-768 - 75.
Simpson AA, Tao Y, Leiman PG, Badasso MO, He Y, Jardine PJ, et al. Structure of the bacteriophage ϕ29 DNA packaging motor. Nature. 2000; 408 :745-750 - 76.
Guasch A, Pous J, Ibarra B, Gomis-Ruth FX, Valpuesta JM, Sousa N, et al. Detailed architecture of a DNA translocating machine: The high-resolution structure of the bacteriophage phi29 connector particle. Journal of Molecular Biology. 2002; 315 :663-676 - 77.
Lebedev AA, Krause MH, Isidro AL, Vagin A, Orlova EV, Turner J, et al. Structural framework for DNA translocation via the viral portal protein. The EMBO Journal. 2007; 26 :1984-1994 - 78.
Olia AS, Prevelige PE Jr, Johnson JE, Cingolani G. Three-dimensional structure of a viral genome-delivery portal vertex. Nature Structural & Molecular Biology. 2011; 18 :597-603 - 79.
Agirrezabala X, Martín-Benito J, Valle M, González JM, Valencia A, Valpuesta JM, et al. Structure of the connector of bacteriophage T7 at 8 Å resolution: Structural homologies of a basic component of a DNA translocating machinery. Journal of Molecular Biology. 2005; 347 :895-902 - 80.
Sun S, Kondabagil K, Draper B, Alam TI, Bowman VD, Zhang Z, et al. The structure of the phage T4 DNA packaging motor suggests a mechanism dependent on electrostatic forces. Cell. 2008; 135 :1251-1262 - 81.
Oliveira L, Tavares P, Alonso JC. Headful DNA packaging: Bacteriophage SPP1 as a model system. Virus Research. 2013; 173 (2):247-259. DOI: 10.1016/j.virusres.2013.01.021 - 82.
Chaban Y, Lurz R, Brasiles S, Cornilleau C, Karreman M, Zinn-Justin S, et al. Structural rearrangements in the phage head-to-tail interface during assembly and infection. Proceedings of the National Academy of Sciences of the United States of America. 2015; 112 :7009-7014 - 83.
Orlova EV, Gowen B, Dröge A, Stiege A, Weise F, Lurz R, et al. Structure of a viral DNA gatekeeper at 10 A resolution by cryoelectron microscopy. The EMBO Journal. 2003; 22 (6):1255-1262 - 84.
Lhuillier S, Gallopin M, Gilquin B, Brasilès S, Lancelot N, Letellier G, et al. Structure of bacteriophage SPP1 head-to-tail connection reveals mechanism for viral DNA gating. Proceedings of the National Academy of Sciences of the United States of America. 2009; 106 (21):8507-8512 - 85.
Plisson C, White HE, Auzat I, Zafarani A, São-Jose C, Lhuillier S, et al. Structure of bacteriophage SPP1 tail reveals trigger for DNA ejection. The EMBO Journal. 2007; 26 :3720-3728 - 86.
Auzat I, Dröge A, Weise F, Lurz R, Tavares P. Origin and function of the two major tail proteins of bacteriophage SPP1. Molecular Microbiology. 2008 Nov; 70 (3):557-569. DOI: 10.1111/j.1365-2958.2008.06435.x - 87.
Cuervo A, Pulido-Cid M, Chagoyen M, Arranz R, González-García VA, Garcia-Doval C, et al. Structural characterization of the bacteriophage T7 tail machinery. The Journal of Biological Chemistry. 2013; 288 :26290-26299 - 88.
Pintilie G, Chen DH, Haase-Pettingell CA, King JA, Chiu W. Resolution and probabilistic models of components in CryoEM maps of mature P22 bacteriophage. Biophysical Journal. 2016; 110 (4):827-839. DOI: 10.1016/j.bpj.2015.11.3522 - 89.
Jiang W, Chang J, Jakana J, Weigele P, King J, Chiu W. Structure of epsilon15 bacteriophage reveals genome organization and DNA packaging/injection apparatus. Nature. 2006; 439 :612-616 - 90.
McElwee M, Vijayakrishnan S, Rixon F, Bhella D. Structure of the herpes simplex virus portal-vertex. PLoS Biology. 2018; 16 (6):e2006191. DOI: 10.1371/journal.pbio.2006191 - 91.
Lander GC, Khayat R, Li R, Prevelige PE, Potter CS, Carragher B, et al. The P22 tail machine at subnanometer resolution. Structure. 2009; 17 (6):789-799 - 92.
Tang J, Lander GC, Olia A, Li R, Casjens S, Prevelige P Jr, et al. Peering down the barrel of a bacteriophage portal: The genome packaging and release valve in p22. Structure. 2011; 19 :496-502 - 93.
Leiman PG, Chipman PR, Kostyuchenko VA, Mesyanzhinov VV, Rossmann MG. Three-dimensional rearrangement of proteins in the tail of bacteriophage T4 on infection of its host. Cell. 2004; 118 :419-429 - 94.
Isidro A, Santos MA, Henriques AO, Tavares P. The high-resolution functional map of bacteriophage SPP1 portal protein. Molecular Microbiology. 2004; 51 :949-962 - 95.
Newcomb WW, Juhas RM, Thomsen DR, Homa FL, Burch AD, Weller SK, et al. The UL6 gene product forms the portal for entry of DNA into the herpes simplex virus capsid. Journal of Virology. 2001; 75 :10923-10932 - 96.
Cardone G, Winkler DC, Trus BL, Cheng N, Heuser JE, Newcomb WW, et al. Visualization of the herpes simplex virus portal in situ by cryo-electron tomography. Virology. 2007; 361 :426-434 - 97.
Arnaud CA, Effantin G, Vives C, Engilberge S, Bacia M, Boulanger P, et al. Bacteriophage T5 tail tube structure suggests a trigger mechanism for Siphoviridae DNA ejection. Nature Communications. 2017; 8 :1953-1953 - 98.
Pell LG, Gasmi-Seabrook GM, Morais M, Neudecker P, Kanelis V, Bona D, et al. The solution structure of the C-terminal Ig-like domain of the bacteriophage λ tail tube protein. Journal of Molecular Biology. 2010; 403 :468-479 - 99.
Effantin G, Boulanger PE, Neumann E, Letellier L, Conway JF. Bacteriophage T5 structure reveals similarities with HK97 and T4 suggesting evolutionary relationships. Journal of Molecular Biology. 2006; 361 :993-1002 - 100.
Papadopoulos S, Smith PR. The structure of the tail of the bacteriophage phi CbK. Journal of Ultrastructure Research. 1982; 80 :62-70 - 101.
Katsura I. Tail Assembly and Injection. Lambda II. Plainview, NY: Cold Spring Harbor; 1983. pp. 331-346 - 102.
Pell LG, Kanelis V, Donaldson LW, Howell PL, Davidson AR. The phage lambda major tail protein structure reveals a common evolution for long-tailed phages and the type VI bacterial secretion system. Proceedings of the National Academy of Sciences of the United States of America. 2009; 106 (11):4160-4165. DOI: 10.1073/pnas.0900044106 - 103.
Pell LG, Liu A, Edmonds L, Donaldson LW, Howell PL, Davidson AR. The X-ray crystal structure of the phage lambda tail terminator protein reveals the biologically relevant hexameric ring structure and demonstrates a conserved mechanism of tail termination among diverse long-tailed phages. Journal of Molecular Biology. 2009; 389 (5):938-951. DOI: 10.1016/j.jmb.2009.04.072. [Epub 2009 May 6] - 104.
Chagot B, Auzat I, Gallopin M, Petitpas I, Gilquin B, Tavares P, et al. Solution structure of gp17 from the Siphoviridae bacteriophage SPP1: Insights into its role in virion assembly. Proteins. 2012; 80 (1):319-326. DOI: 10.1002/prot.23191 - 105.
Xiang Y, Leiman PG, Li L, Grimes S, Anderson DL, Rossmann MG. Crystallographic insights into the autocatalytic assembly mechanism of a bacteriophage tailspike. Molecular Cell. 2009; 34 :375-386. DOI: 10.1016/j.molcel.2009.04.009 - 106.
Xu J, Gui M, Wang D, Xiang Y. The bacteriophage φ29 tail possesses a pore-forming loop for cell membrane penetration. Nature. 2016; 534 :544-547 - 107.
Garcia-Doval C, Castón JR, Luque D, Granell M, Otero JM, Llamas-Saiz AL, et al. Conformational changes leading to T7 DNA delivery upon interaction with the bacterial receptor. Viruses. 2015; 7 (12):6424-6440. DOI: 10.3390/v7122946 - 108.
Steinbacher S, Baxa U, Miller S, Weintraub A, Seckler R, Huber R. Crystal structure of phage P22 tailspike protein complexed with Salmonella sp. O-antigen receptors. Proceedings of the National Academy of Sciences of the United States of America. 1996;93 (20):10584-10588 - 109.
Steinbacher S, Miller S, Baxa U, Budisa N, Weintraub A, Seckler R, et al. Phage P22 tailspike protein: crystal structure of the head-binding domain at 2.3 Å, fully refined structure of the endorhamnosidase at 1.56 Å resolution, and the molecular basis of O-antigen recognition and cleavage. Journal of Molecular Biology. 1997; 267 :865-880 - 110.
Chang JT, Schmid MF, Haase-Pettingell C, Weigele PR, King JA, Chiu W. Visualizing the structural changes of bacteriophage Epsilon15 and its Salmonella host during infection. Journal of Molecular Biology. 2010; 402 (4):731-740. DOI: 10.1016/j.jmb.2010.07.058 - 111.
Taylor NM, Prokhorov NS, Guerrero-Ferreira RC, Shneider MM, Browning C, Goldie KN, et al. Structure of the T4 baseplate and its function in triggering sheath contraction. Nature. 2016; 533 :346-352 - 112.
Zheng W, Wang F, Taylor NMI, Guerrero-Ferreira RC, Leiman PG, Egelman EE. Refined Cryo-EM structure of the T4 tail tube: Exploring the lowest dose limit. Structure. 2017; 25 :1436-1441 - 113.
Fokine A, Zhang Z, Kanamaru S, Bowman VD, Aksyuk AA, Arisaka F, et al. The molecular architecture of the bacteriophage T4 neck. Journal of Molecular Biology. 2013; 425 :1731-1744 - 114.
Aksyuk AA, Leiman PG, Shneider MM, Mesyanzhinov VV, Rossmann MG. The structure of gene product 6 of bacteriophage T4, the hinge-pin of the baseplate. Structure. 2009; 17 :800-808 - 115.
Aksyuk AA, Kurochkina LP, Fokine A, Forouhar F, Mesyanzhinov VV, Tong L, et al. Structural conservation of the Myoviridae phage tail sheath protein fold. Structure. 2011;19 :1885-1894 - 116.
Veesler D, Cambillau C. A common evolutionary origin for tailed bacteriophage functional modules and bacterial machineries. Microbiology and Molecular Biology Reviews. 2011; 75 :423-433 - 117.
Davidson AR, Cardarelli L, Pell LG, Radford DR, Maxwell KL. Long noncontractile tail machines of bacteriophages. Advances in Experimental Medicine and Biology. 2012; 726 :115-142. DOI: 10.1007/978-1-4614-0980-9_6 - 118.
Veesler D, Robin G, Lichière J, Auzat I, Tavares P, Bron P, et al. Crystal structure of bacteriophage SPP1 distal tail protein (gp19.1): A baseplate hub paradigm in Gram-positive infecting phages. The Journal of Biological Chemistry. 2010; 285 :36666-36673 - 119.
Xiang Y, Morais MC, Cohen DN, Bowman VD, Anderson DL, Rossmann MG. Crystal and cryoEM structural studies of a cell wall degrading enzyme in the bacteriophage phi29 tail. Proceedings of the National Academy of Sciences of the United States of America. 2008; 105 (28):9552-9557. DOI: 10.1073/pnas.0803787105 - 120.
Tang L, Marion WR, Cingolani G, Prevelige PE, Johnson JE. Three-dimensional structure of the bacteriophage P22 tail machine. The EMBO Journal. 2005; 24 :2087-2095 - 121.
Chang J, Weigele P, King J, Chiu W, Jiang W. Cryo-EM asymmetric reconstruction of bacteriophage P22 reveals organization of its DNA packaging and infecting machinery. Structure. 2006; 14 (6):1073-1082 - 122.
Tang L, Gilcrease EB, Casjens SR, Johnson JE. Highly discriminatory binding of capsid-cementing proteins in bacteriophage L. Structure. 2006; 14 (5):837-845 - 123.
Olia AS, Casjens S, Cingolani G. Structure of phage P22 cell envelope-penetrating needle. Nature Structural & Molecular Biology. 2007; 14 (12):1221-1226 - 124.
Steinbacher S, Seckler R, Miller S, Steipe B, Huber R, Reinemer P. Crystal structure of P22 tailspike protein: Interdigitated subunits in a thermostable trimer. Science. 1994; 265 :383-386 - 125.
Sciara G, Bebeacua C, Bron P, Tremblay D, Ortiz-Lombardia M, Lichière J, et al. Structure of lactococcal phage p2 baseplate and its mechanism of activation. Proceedings of the National Academy of Sciences of the United States of America. 2010; 107 :6852-6857 - 126.
Veesler D, Spinelli S, Mahony J, Lichière J, Blangy S, Bricogne G, et al. Structure of the phage TP901-1 1.8MDabaseplate suggests an alternative host adhesion mechanism. Proceedings of the National Academy of Sciences of the United States of America. 2012; 109 :8954-8958. DOI: 10.1073/pnas.1200966109 - 127.
Flayhan A, Vellieux FM, Lurz R, Maury O, Contreras-Martel C, Girard E, et al. Crystal structure of pb9, the distal tail protein of bacteriophage T5: A conserved structural motif among all siphophages. Journal of Virology. 2014; 88 :820-828 - 128.
Zivanovic Y, Confalonieri F, Ponchon L, Lurz R, Chami M, Flayhan A, et al. Insights into bacteriophage T5 structure from analysis of its morphogenesis genes and protein components. Journal of Virology. 2014; 88 :1162-1174 - 129.
Mitraki A, Papanikolopoulou K, van Raaij MJ. Natural triple β-stranded fibrous folds. Advances in Protein Chemistry. 2006; 73 :97-124 - 130.
Parent KN, Gilcrease EB, Casjens SR, Baker TS. Structural evolution of the P22-like phages: comparison of Sf6 and P22 procapsid and virion architectures. Virology. 2012; 427 :177-188 - 131.
Barbirz S, Muller JJ, Uetrecht C, Clark AJ, Heinemann U, Seckler R. Crystal structure of Escherichia coli phage HK620 tailspike: Podoviral tailspike endoglycosidase modules are evolutionarily related. Molecular Microbiology. 2008;69 :303-316 - 132.
Rajagopala SV, Casjens S, Uetz P. The protein interaction map of bacteriophage lambda. BMC Microbiology. 2011; 11 :213 - 133.
Morais MC, Tao Y, Olson NH, Grimes S, Jardine PJ, Anderson DL, et al. Cryoelectron-microscopy image reconstruction of symmetry mismatches in bacteriophage φ29. Journal of Structural Biology. 2001; 135 :38-46 - 134.
Farley MM, Tu J, Kearns DB, Molineux IJ, Liu J. Ultrastructural analysis of bacteriophage Φ29 during infection of Bacillus subtilis . Journal of Structural Biology. 2017;197 (2):163-171. DOI: 10.1016/j.jsb.2016.07.019 - 135.
Tao Y, Olson NH, Xu W, Anderson DL, Rossmann MG, Baker TS. Assembly of a tailed bacterial virus and its genome release studied in three dimensions. Cell. 1998; 95 :431-437 - 136.
Leiman PG, Kanamaru S, Mesyanzhinov VV, Arisaka F, Rossmann MG. Structure and morphogenesis of bacteriophage T4. Cellular and Molecular Life Sciences. 2003; 60 (11):2356-2370 - 137.
Leiman PG, Arisaka F, van Raaij MJ, Kostyuchenko VA, Aksyuk AA, Kanamaru S, et al. Morphogenesis of the T4 tail and tail fibers. Virology Journal. 2010; 7 :355. DOI: 10.1186/1743-422X-7-355 - 138.
Arisaka F, Yap ML, Kanamaru S, Rossmann MG. Molecular assembly and structure of the bacteriophage T4 tail. Biophysical Reviews. 2016; 8 (4):385-396. DOI: 10.1007/s12551-016-0230-x - 139.
Crawford JT, Goldberg EB. The function of tail fibers in triggering baseplate expansion of bacteriophage T4. Journal of Molecular Biology. 1980; 139 (4):679-690 - 140.
Kostyuchenko VA, Leiman PG, Chipman PR, Kanamaru S, van Raaij MJ, Arisaka F, et al. Three-dimensional structure of bacteriophage T4 baseplate. Nature Structural Biology. 2003; 10 (9):688-693 - 141.
Yap ML, Rossmann MG. Structure and function of bacteriophage T4. Future Microbiology. 2014; 9 (12):1319-1327. DOI: 10.2217/fmb.14.91 - 142.
Yap ML, Klose T, Arisaka F, Speirc JA, Veeslerc D, Fokine A, et al. The role of bacteriophage T4 baseplate in regulating assembly and infection. Proceedings of the National Academy of Sciences of the United States of America. 2016; 113 (10):2654-2659 - 143.
Kanamaru S, Leiman PG, Kostyuchenko VA, Chipman PR, Mesyanzhinov VV, Arisaka F, et al. Structure of the cell-puncturing device of bacteriophage T4. Nature. 2002; 415 :553-557. DOI: 10.1038/415553a - 144.
Shneider MM, Buth SA, Ho BT, Basler M, Mekalanos JJ, Leiman PG. PAAR-repeat proteins sharpen and diversify the type VI secretion system spike. Nature. 2013; 500 :350-353. DOI: 10.1038/nature1245 - 145.
Tavares P, Zinn-Justin S, Orlova EV. Genome gating in tailed bacteriophage capsids. Advances in Experimental Medicine and Biology. 2012; 726 :585-600. DOI: 10.1007/978-1-4614-0980-9_25. [Review. PMID: 22297531] - 146.
Ando H, Lemire S, Pires DP, Lu TK. Engineering modular viral scaffolds for targeted bacterial population editing. Cell Systems. 2015; 1 (3):187-196 - 147.
Abedon ST. Ecology of anti-biofilm agents II: Bacteriophage exploitation and biocontrol of biofilm bacteria. Pharmaceuticals (Basel). 2015; 8 (3):559-589. DOI: 10.3390/ph8030559
Notes
- chem.ch.huji.ac.il/nmr/whatisnmr/whatisnmr.html