7UN3

Complex of UBE2O with NAP1L1 and ubiquitylated uL2

7UN3 の概要

• エントリーDOI: 10.2210/pdb7un3/pdb
• EMDBエントリー: 26612
• 分子名称: Ubiquitin,60S ribosomal protein L8,(E3-independent) E2 ubiquitin-conjugating enzyme fusion, Nucleosome assembly protein 1-like 1 (2 entities in total)
• 機能のキーワード: ubiquitylation, cytosolic protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 478184.61

構造登録者

Yip, M.C.J.,Sedor, S.F.,Shao, S. (登録日: 2022-04-08, 公開日: 2022-08-03, 最終更新日: 2024-02-14)

主引用文献

Yip, M.C.J.,Sedor, S.F.,Shao, S.
Mechanism of client selection by the protein quality-control factor UBE2O.
Nat.Struct.Mol.Biol., 29:774-780, 2022

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. 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.

PubMed: 35915257
DOI: 10.1038/s41594-022-00807-6

実験手法

ELECTRON MICROSCOPY (3.5 Å)