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-Structure paper
Title | Mechanism of client selection by the protein quality-control factor UBE2O. |
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Journal, issue, pages | Nat Struct Mol Biol, Vol. 29, Issue 8, Page 774-780, Year 2022 |
Publish date | Aug 1, 2022 |
Authors | Matthew C J Yip / Samantha F Sedor / Sichen Shao / |
PubMed Abstract | 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. |
External links | Nat Struct Mol Biol / PubMed:35915257 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.3 - 3.5 Å |
Structure data | EMDB-26612, PDB-7un3: EMDB-26614, PDB-7un6: EMDB-26615: Complex of UBE2O with NAP1L1 and ubiquitylated uL2 (focused on UBE2O-Ub) |
Source |
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Keywords | CYTOSOLIC PROTEIN / Ubiquitylation |