title: Ubiquitin transfer from the E2 perspective: why is UbcH5 so promiscuous?
abstract: Protein ubiquitination is a regulatory process that influences nearly every aspect of eukaryotic cell biology. Pathways that range from cell-cycle progression and differentiation to DNA repair to vesicle budding all rely on regulated modification of target proteins by ubiquitin. Target proteins can be tagged by a single molecule of ubiquitin or modified by ubiquitin polymers that can vary in length and linkage specificity, and these variations influence how ubiquitination signals are interpreted. Surprisingly, little is understood regarding mechanisms of protein ubiquitination and how poly-ubiquitin chains are synthesized. Simple models to explain ubiquitin transfer have dominated the literature, but recent work suggests basic assumptions as to how proteins assemble to facilitate protein ubiquitination and poly-ubiquitin chain synthesis should be reexamined. This is particularly necessary for understanding the roles played by E2 ubiquitin-conjugating enzymes, a central protein component in all ubiquitin transfer reactions. In particular, UbcH5, a canonical E2 protein that is active in a broad number of in vitro ubiquitin transfer reactions, is capable of binding ubiquitin noncovalently on a surface distinct from its active site. This unique property allows activated UbcH5 approximately Ub complexes to self-assemble and has a profound influence on poly-ubiquitin chain synthesis.
authors.affiliation: Department of Biochemistry, University of Washington, Seattle, Washington 98195-7742, USA.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Brzovic
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Klevit
mesh_terms: D000595:Amino Acid Sequence; D019313:BRCA1 Protein / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D014157:Transcription Factors / Q000737:chemistry; D025801:Ubiquitin / Q000378:metabolism*; D044763:Ubiquitin-Conjugating Enzymes / Q000737:chemistry / Q000378:metabolism*
chemical_list: D019313:BRCA1 Protein; D014157:Transcription Factors; D025801:Ubiquitin; D044763:Ubiquitin-Conjugating Enzymes