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-Structure paper
タイトル | Mechanism of client selection by the protein quality-control factor UBE2O. |
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ジャーナル・号・ページ | Nat Struct Mol Biol, Vol. 29, Issue 8, Page 774-780, Year 2022 |
掲載日 | 2022年8月1日 |
著者 | Matthew C J Yip / Samantha F Sedor / Sichen Shao / |
PubMed 要旨 | The E2/E3 enzyme UBE2O ubiquitylates diverse clients to mediate important processes, including targeting unassembled 'orphan' proteins for quality control and clearing ribosomes during erythropoiesis. ...The E2/E3 enzyme UBE2O ubiquitylates diverse clients to mediate important processes, including targeting unassembled 'orphan' proteins for quality control and clearing ribosomes during erythropoiesis. How quality-control factors, such as UBE2O, select clients on the basis of heterogeneous features is largely unknown. Here, we show that UBE2O client selection is regulated by ubiquitin binding and a cofactor, NAP1L1. Attaching a single ubiquitin onto a client enhances UBE2O binding and multi-mono-ubiquitylation. UBE2O also repurposes the histone chaperone NAP1L1 as an adapter to recruit a subset of clients. Cryo-EM structures of human UBE2O in complex with NAP1L1 reveal a malleable client recruitment interface that is autoinhibited by the intrinsically reactive UBC domain. Adding a ubiquitylated client identifies a distinct ubiquitin-binding SH3-like domain required for client selection. Our findings reveal how multivalency and a feed-forward mechanism drive the selection of protein quality-control clients. |
リンク | Nat Struct Mol Biol / PubMed:35915257 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.3 - 3.5 Å |
構造データ | EMDB-26612, PDB-7un3: EMDB-26614, PDB-7un6: EMDB-26615: Complex of UBE2O with NAP1L1 and ubiquitylated uL2 (focused on UBE2O-Ub) |
由来 |
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キーワード | CYTOSOLIC PROTEIN (細胞質基質) / Ubiquitylation (ユビキチン) |