Protein ubiquitination is an essential cellular process that maintains protein homeostasis, regulates protein, and cell functions, and removes aggregated and misfolded protein. Disruption in function of any of the protein components of the ubiquitination pathway is associated with human diseases including cancers. An important member in the ubiquitination cascade is the very large E3 ligase family that directs substrate modification. The RING-type E3 ligases possess a cysteine/histidine-rich zinc-binding RING domain that confers ligase functionality. RING domains adopt a canonical ββα-fold. TRIM proteins represent a novel class of RING-type E3 ligase. TRIM proteins consist of an N-terminal RING domain followed by one or two B-box domains. The two types of B-box domains play essential roles in protein ubiquitination by contributing to substrate targeting, ligase activity enhancement, and redundancy of ligase activity. This review presents a general background of the B-box domains, a structural and functional comparison with RING domains, and a summary of recent work demonstrating their role in proteolysis. We discuss new findings that reveal B-box domains which are ubiquitous and are found in non-TRIM plant proteins without the adjacent RING domain, indicating that B-boxes are members of RING-class E3 ligases.
Part of the book: Ubiquitin Proteasome System