8OR2

CAND1-CUL1-RBX1-DCNL1

8OR2 の概要

• エントリーDOI: 10.2210/pdb8or2/pdb
• 関連するPDBエントリー: 8OR0 8OR3 8OR4
• EMDBエントリー: 17115
• 分子名称: Cullin-1, E3 ubiquitin-protein ligase RBX1, Cullin-associated NEDD8-dissociated protein 1, ... (5 entities in total)
• 機能のキーワード: cand1, substrate receptor exchange factor, cullin-ring ligase, crl, scf, ligase, neddylation, dcnl1 co-e3, ubiquitin signaling
• 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: 273879.53

構造登録者

Shaaban, M.,Clapperton, J.A.,Ding, S.,Maeots, M.E.,Enchev, R.I. (登録日: 2023-04-12, 公開日: 2023-06-28, 最終更新日: 2024-07-24)

主引用文献

Shaaban, M.,Clapperton, J.A.,Ding, S.,Kunzelmann, S.,Maeots, M.E.,Maslen, S.L.,Skehel, J.M.,Enchev, R.I.
Structural and mechanistic insights into the CAND1-mediated SCF substrate receptor exchange.
Mol.Cell, 83:2332-, 2023

PubMed Abstract: Modular SCF (SKP1-CUL1-Fbox) ubiquitin E3 ligases orchestrate multiple cellular pathways in eukaryotes. Their variable SKP1-Fbox substrate receptor (SR) modules enable regulated substrate recruitment and subsequent proteasomal degradation. CAND proteins are essential for the efficient and timely exchange of SRs. To gain structural understanding of the underlying molecular mechanism, we reconstituted a human CAND1-driven exchange reaction of substrate-bound SCF alongside its co-E3 ligase DCNL1 and visualized it by cryo-EM. We describe high-resolution structural intermediates, including a ternary CAND1-SCF complex, as well as conformational and compositional intermediates representing SR- or CAND1-dissociation. We describe in molecular detail how CAND1-induced conformational changes in CUL1/RBX1 provide an optimized DCNL1-binding site and reveal an unexpected dual role for DCNL1 in CAND1-SCF dynamics. Moreover, a partially dissociated CAND1-SCF conformation accommodates cullin neddylation, leading to CAND1 displacement. Our structural findings, together with functional biochemical assays, help formulate a detailed model for CAND-SCF regulation.

PubMed: 37339624
DOI: 10.1016/j.molcel.2023.05.034

実験手法

ELECTRON MICROSCOPY (3.2 Å)