8JRI

Cryo-EM structure of human 26S proteasomal RP subcomplex (Ea state) without any bound substrate.

8JRI の概要

• エントリーDOI: 10.2210/pdb8jri/pdb
• EMDBエントリー: 36598
• 分子名称: 26S protease regulatory subunit 7, Proteasome subunit alpha type-1, Proteasome subunit alpha type-3, ... (28 entities in total)
• 機能のキーワード: protein degradation, macromolecular complex, ubiquitin-proteasome system, cytosolic protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 25
• 化学式量合計: 1099782.78

構造登録者

Hsu, S.T.D.,Draczkowski, P.,Wang, Y.S. (登録日: 2023-06-16, 公開日: 2024-12-18, 最終更新日: 2025-11-05)

主引用文献

Draczkowski, P.,Chen, S.N.,Chen, T.,Wang, Y.S.,Shih, H.A.,Huang, J.Y.C.,Tsai, M.C.,Lin, S.Y.,Lin, S.,Viner, R.,Chang, Y.C.,Wu, K.P.,Hsu, S.D.
Structural basis of K11/K48-branched ubiquitin chain recognition by the human 26S proteasome.
Nat Commun, 16:9094-9094, 2025

PubMed Abstract: Beyond the canonical K48-linked homotypic polyubiquitination for proteasome-targeted proteolysis, K11/K48-branched ubiquitin (Ub) chains are involved in fast-tracking protein turnover during cell cycle progression and proteotoxic stress. Here, we report cryo-EM structures of human 26S proteasome in a complex with a K11/K48-branched Ub chain. The structures revealed a multivalent substrate recognition mechanism involving a hitherto unknown K11-linked Ub binding site at the groove formed by RPN2 and RPN10 in addition to the canonical K48-linkage binding site formed by RPN10 and RPT4/5 coiled-coil. Additionally, RPN2 recognizes an alternating K11-K48-linkage through a conserved motif similar to the K48-specific T1 binding site of RPN1. The insights gleaned from these structures explain the molecular mechanism underlying the recognition of the K11/K48-branched Ub as a priority signal in the ubiquitin-mediated proteasomal degradation.

PubMed: 41093839
DOI: 10.1038/s41467-025-64719-x

実験手法

ELECTRON MICROSCOPY (3.4 Å)