6op8
From Proteopedia
S. pombe Ubc7/U7BR complex
Structural highlights
FunctionUBC7_SCHPO Catalyzes the covalent attachment of ubiquitin to other proteins. Functions in degradation of misfolded or regulated proteins localized in the endoplasmic reticulum (ER) lumen or membrane via the ubiquitin-proteasome system. Cognate E2 conjugating enzyme for the doa10 ubiquitin ligase complex, which is part of the ERAD-C pathway responsible for the rapid degradation of membrane proteins with misfolded cytoplasmic domains, and of the hrd1 ubiquitin ligase complex, which is part of the ERAD-L and ERAD-M pathways responsible for the rapid degradation of soluble lumenal and membrane proteins with misfolded lumenal domains (ERAD-L), or ER-membrane proteins with misfolded transmembrane domains (ERAD-M) (By similarity). Together with hrd1, required for the degradation of the transcription factor sre1 precursor in the absence of its binding partner scp1. Has a role in the formation of chromatin structures that influence the localization of transcriptional silencing factors.[PROSITE-ProRule:PRU00388][1] [2] Publication Abstract from PubMedEndoplasmic reticulum (ER)-associated degradation (ERAD) is a protein quality-control pathway in eukaryotes in which misfolded ER proteins are polyubiquitylated, extracted and ultimately degraded by the proteasome. This process involves ER membrane-embedded ubiquitin E2 and E3 enzymes, as well as a soluble E2 enzyme (Ubc7 in Saccharomyces cerevisiae and UBE2G2 in mammals). E2-binding regions (E2BRs) that recruit these soluble ERAD E2s to the ER have been identified in humans and S. cerevisiae, and structures of E2-E2BR complexes from both species have been determined. In addition to sequence and structural differences between the human and S. cerevisiae E2BRs, the binding of E2BRs also elicits different biochemical outcomes with respect to E2 charging by E1 and E2 discharge. Here, the Schizosaccharomyces pombe E2BR was identified and purified with Ubc7 to resolve a 1.7 A resolution co-crystal structure of the E2BR in complex with Ubc7. The S. pombe E2BR binds to the back side of the E2 as an alpha-helix and, while differences exist, it exhibits greater similarity to the human E2BR. Structure-based sequence alignments reveal differences and conserved elements among these species. Structural comparisons and biochemistry reveal that the S. pombe E2BR presents a steric impediment to E1 binding and inhibits E1-mediated charging, respectively. Crystal structure of the Schizosaccharomyces pombe U7BR E2-binding region in complex with Ubc7.,Hann ZS, Metzger MB, Weissman AM, Lima CD Acta Crystallogr F Struct Biol Commun. 2019 Aug 1;75(Pt 8):552-560. doi:, 10.1107/S2053230X19009786. Epub 2019 Aug 2. PMID:31397327[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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