9QO5

Dissociation-state-4 of 9-subunit CSN and SCF (SKP1-SKP2-CKS1) complex

9QO5 の概要

• エントリーDOI: 10.2210/pdb9qo5/pdb
• EMDBエントリー: 53257
• 分子名称: COP9 signalosome complex subunit 1, S-phase kinase-associated protein 1, S-phase kinase-associated protein 2, ... (17 entities in total)
• 機能のキーワード: e3 ligases, cop9 signalosome, ligase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 14
• 化学式量合計: 513393.78

構造登録者

Ding, S.,Clapperton, J.A.,Maeots, M.E.,Enchev, R.I. (登録日: 2025-03-25, 公開日: 2026-02-04, 最終更新日: 2026-02-18)

主引用文献

Ding, S.,Clapperton, J.A.,Maeots, M.E.,Kunzelmann, S.,Shaaban, M.,Enchev, R.I.
Structural basis of CSN-mediated SCF deneddylation.
Nat Commun, 17:951-951, 2026

PubMed Abstract: Cullin-RING ligases (CRLs) are the largest family of E3 ligases, with ubiquitination activity dynamically regulated by neddylation and deneddylation by the COP9 signalosome (CSN). CSN-mediated deneddylation not only deactivates CRLs but also enables substrate receptor exchange. Although CSN is a promising drug target, the structural basis underlying its catalytic mechanism remains unclear. Here, we use cryo-electron microscopy (cryo-EM) to uncover distinct functional states of CSN-CRL (SCF) complexes, capturing key intermediates of the deneddylation cycle. We visualise an autoinhibited docking state and a catalytic intermediate in which CSN5 Ins-1 loop, RBX1 RING and neddylated Cullin WHB domains are repositioned for isopeptide cleavage. We further resolve four dissociation intermediates that define the stepwise release of CSN from its product, with RBX1 RING stabilising key interactions. Additionally, our structures locate CSNAP within a CSN3-CSN8 groove. Together, our study provides a mechanistic model for CSN function and informs the rational design of CSN-targeted therapeutics.

PubMed: 41577659
DOI: 10.1038/s41467-025-67566-y

実験手法

ELECTRON MICROSCOPY (4 Å)