6R6H

Structural basis of Cullin-2 RING E3 ligase regulation by the COP9 signalosome

6R6H の概要

• エントリーDOI: 10.2210/pdb6r6h/pdb
• EMDBエントリー: 4736
• 分子名称: COP9 signalosome complex subunit 1, ELOC_HUMAN, RBX1_HUMAN, ... (14 entities in total)
• 機能のキーワード: cullin-ring e3 ligase cop9 signalosome neddylation, ligase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 13
• 化学式量合計: 455958.20

構造登録者

Morris, E.P.,Faull, S.V.,Lau, A.M.C.,Politis, A.,Beuron, F.,Cronin, N. (登録日: 2019-03-27, 公開日: 2019-08-28, 最終更新日: 2024-05-22)

主引用文献

Faull, S.V.,Lau, A.M.C.,Martens, C.,Ahdash, Z.,Hansen, K.,Yebenes, H.,Schmidt, C.,Beuron, F.,Cronin, N.B.,Morris, E.P.,Politis, A.
Structural basis of Cullin 2 RING E3 ligase regulation by the COP9 signalosome.
Nat Commun, 10:3814-3814, 2019

PubMed Abstract: Cullin-Ring E3 Ligases (CRLs) regulate a multitude of cellular pathways through specific substrate receptors. The COP9 signalosome (CSN) deactivates CRLs by removing NEDD8 from activated Cullins. Here we present structures of the neddylated and deneddylated CSN-CRL2 complexes by combining single-particle cryo-electron microscopy (cryo-EM) with chemical cross-linking mass spectrometry (XL-MS). These structures suggest a conserved mechanism of CSN activation, consisting of conformational clamping of the CRL2 substrate by CSN2/CSN4, release of the catalytic CSN5/CSN6 heterodimer and finally activation of the CSN5 deneddylation machinery. Using hydrogen-deuterium exchange (HDX)-MS we show that CRL2 activates CSN5/CSN6 in a neddylation-independent manner. The presence of NEDD8 is required to activate the CSN5 active site. Overall, by synergising cryo-EM with MS, we identify sensory regions of the CSN that mediate its stepwise activation and provide a framework for understanding the regulatory mechanism of other Cullin family members.

PubMed: 31444342
DOI: 10.1038/s41467-019-11772-y

実験手法

ELECTRON MICROSCOPY (8.4 Å)