6WCQ

Structure of a substrate-bound DQC ubiquitin ligase

6WCQ の概要

• エントリーDOI: 10.2210/pdb6wcq/pdb
• 関連するPDBエントリー: 6W66
• EMDBエントリー: 21617
• 分子名称: S-phase kinase-associated protein 1, F-box/LRR-repeat protein 17, Kelch-like ECH-associated protein 1, ... (4 entities in total)
• 機能のキーワード: ubiquitin, e3-ligase, multiprotein complex, substrate recognition, ligase
• 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: 183750.01

構造登録者

Mena, E.L.,Jevtic, P.,Greber, B.J.,Gee, C.L.,Lew, B.G.,Akopian, D.,Nogales, E.,Kuriyan, J.,Rape, M. (登録日: 2020-03-31, 公開日: 2020-08-19, 最終更新日: 2024-03-06)

主引用文献

Mena, E.L.,Jevtic, P.,Greber, B.J.,Gee, C.L.,Lew, B.G.,Akopian, D.,Nogales, E.,Kuriyan, J.,Rape, M.
Structural basis for dimerization quality control.
Nature, 586:452-456, 2020

PubMed Abstract: Most quality control pathways target misfolded proteins to prevent toxic aggregation and neurodegeneration. Dimerization quality control further improves proteostasis by eliminating complexes of aberrant composition, but how it detects incorrect subunits remains unknown. Here we provide structural insight into target selection by SCF-FBXL17, a dimerization-quality-control E3 ligase that ubiquitylates and helps to degrade inactive heterodimers of BTB proteins while sparing functional homodimers. We find that SCF-FBXL17 disrupts aberrant BTB dimers that fail to stabilize an intermolecular β-sheet around a highly divergent β-strand of the BTB domain. Complex dissociation allows SCF-FBXL17 to wrap around a single BTB domain, resulting in robust ubiquitylation. SCF-FBXL17 therefore probes both shape and complementarity of BTB domains, a mechanism that is well suited to establish quality control of complex composition for recurrent interaction modules.

PubMed: 32814905
DOI: 10.1038/s41586-020-2636-7

実験手法

ELECTRON MICROSCOPY (8.5 Å)