7OWD

Structure of CYLD CAP-Gly3 (467-552) bound to Ub; tetragonal space group

7OWD の概要

• エントリーDOI: 10.2210/pdb7owd/pdb
• 関連するPDBエントリー: 7OWC
• 分子名称: Ubiquitin carboxyl-terminal hydrolase CYLD, Ubiquitin (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: 2
• 化学式量合計: 17961.56

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

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

実験手法

X-RAY DIFFRACTION (1.71 Å)