8CDK

CAND1 b-hairpin++-SCF-SKP2 CAND1 partly engaged SCF partly rocked

8CDK の概要

• エントリーDOI: 10.2210/pdb8cdk/pdb
• EMDBエントリー: 16576
• 分子名称: Cullin-1, Cullin-associated NEDD8-dissociated protein 1, E3 ubiquitin-protein ligase RBX1, N-terminally processed, ... (6 entities in total)
• 機能のキーワード: cullin-ring e3 ubiquitin ligase, scf, cand1, assembly factor, ligase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 306200.44

構造登録者

Baek, K.,Schulman, B.A. (登録日: 2023-01-31, 公開日: 2023-04-19, 最終更新日: 2025-07-09)

主引用文献

Baek, K.,Scott, D.C.,Henneberg, L.T.,King, M.T.,Mann, M.,Schulman, B.A.
Systemwide disassembly and assembly of SCF ubiquitin ligase complexes.
Cell, 186:1895-, 2023

PubMed Abstract: Cells respond to environmental cues by remodeling their inventories of multiprotein complexes. Cellular repertoires of SCF (SKP1-CUL1-F box protein) ubiquitin ligase complexes, which mediate much protein degradation, require CAND1 to distribute the limiting CUL1 subunit across the family of ∼70 different F box proteins. Yet, how a single factor coordinately assembles numerous distinct multiprotein complexes remains unknown. We obtained cryo-EM structures of CAND1-bound SCF complexes in multiple states and correlated mutational effects on structures, biochemistry, and cellular assays. The data suggest that CAND1 clasps idling catalytic domains of an inactive SCF, rolls around, and allosterically rocks and destabilizes the SCF. New SCF production proceeds in reverse, through SKP1-F box allosterically destabilizing CAND1. The CAND1-SCF conformational ensemble recycles CUL1 from inactive complexes, fueling mixing and matching of SCF parts for E3 activation in response to substrate availability. Our data reveal biogenesis of a predominant family of E3 ligases, and the molecular basis for systemwide multiprotein complex assembly.

PubMed: 37028429
DOI: 10.1016/j.cell.2023.02.035

実験手法

ELECTRON MICROSCOPY (3.32 Å)