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7OWC

Structure of CYLD CAP-Gly3 (467-565) bound to Ub; orthorhobic space group

7OWC の概要
エントリーDOI10.2210/pdb7owc/pdb
分子名称Ubiquitin-60S ribosomal protein L40, Deubiquitinating enzyme CYLD (3 entities in total)
機能のキーワードubiquitin binding domain, deubiquitinating enzyme, immune system
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38533.96
構造登録者
Elliott, P.R.,Komander, D. (登録日: 2021-06-17, 公開日: 2021-10-20, 最終更新日: 2024-01-31)
主引用文献Elliott, P.R.,Leske, D.,Wagstaff, J.,Schlicher, L.,Berridge, G.,Maslen, S.,Timmermann, F.,Ma, B.,Fischer, R.,Freund, S.M.V.,Komander, D.,Gyrd-Hansen, M.
Regulation of CYLD activity and specificity by phosphorylation and ubiquitin-binding CAP-Gly domains.
Cell Rep, 37:109777-109777, 2021
Cited by
PubMed Abstract: Non-degradative ubiquitin chains and phosphorylation events govern signaling responses by innate immune receptors. The deubiquitinase CYLD in complex with SPATA2 is recruited to receptor signaling complexes by the ubiquitin ligase LUBAC and regulates Met1- and Lys63-linked polyubiquitin and receptor signaling outcomes. Here, we investigate the molecular determinants of CYLD activity. We reveal that two CAP-Gly domains in CYLD are ubiquitin-binding domains and demonstrate a requirement of CAP-Gly3 for CYLD activity and regulation of immune receptor signaling. Moreover, we identify a phosphorylation switch outside of the catalytic USP domain, which activates CYLD toward Lys63-linked polyubiquitin. The phosphorylated residue Ser568 is a novel tumor necrosis factor (TNF)-regulated phosphorylation site in CYLD and works in concert with Ser418 to enable CYLD-mediated deubiquitination and immune receptor signaling. We propose that phosphorylated CYLD, together with SPATA2 and LUBAC, functions as a ubiquitin-editing complex that balances Lys63- and Met1-linked polyubiquitin at receptor signaling complexes to promote LUBAC signaling.
PubMed: 34610306
DOI: 10.1016/j.celrep.2021.109777
主引用文献が同じPDBエントリー
実験手法
X-RAY DIFFRACTION (1.85 Å)
構造検証レポート
Validation report summary of 7owc
検証レポート(詳細版)ダウンロードをダウンロード

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件を2024-10-30に公開中

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