9PDN

Nub1/Fat10-processing human 26S proteasome with Rpt1 at top of spiral staircase (AAA+ locally refined)

これはPDB形式変換不可エントリーです。

9PDN の概要

• エントリーDOI: 10.2210/pdb9pdn/pdb
• EMDBエントリー: 71538
• 分子名称: 26S protease regulatory subunit 8, Substrate polypeptide, 26S proteasome regulatory subunit 7, ... (19 entities in total)
• 機能のキーワード: 26s proteasome, nub1, fat10, motor protein, hydrolase-protein binding complex
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 15
• 化学式量合計: 530928.77

構造登録者

Arkinson, C.,Gee, C.L.,Martin, A. (登録日: 2025-06-30, 公開日: 2025-11-19, 最終更新日: 2025-12-24)

主引用文献

Arkinson, C.,Gee, C.L.,Zhang, Z.,Dong, K.C.,Martin, A.
Structural landscape of the degrading 26S proteasome reveals conformation-specific binding of TXNL1.
Nat.Struct.Mol.Biol., 32:2403-2415, 2025

PubMed Abstract: The 26S proteasome targets many cellular proteins for degradation during homeostasis and quality control. Proteasome-interacting cofactors modulate these functions and aid in substrate degradation. Here we solve high-resolution structures of the redox active cofactor TXNL1 bound to the human 26S proteasome at saturating and substoichiometric concentrations by time-resolved cryo-electron microscopy (cryo-EM). We identify distinct binding modes of TXNL1 that depend on the proteasome conformation and ATPase motor states. Together with biophysical and biochemical experiments, we show that the resting-state proteasome binds TXNL1 with low affinity and in variable positions on top of the Rpn11 deubiquitinase. In contrast, in the actively degrading proteasome, TXNL1 uses additional interactions for high-affinity binding, whereby its C-terminal tail covers the catalytic groove of Rpn11 and coordinates the active-site Zn. Furthermore, these cryo-EM structures of the degrading proteasome capture the ATPase hexamer in several spiral-staircase arrangements that indicate temporally asymmetric hydrolysis and conformational changes in bursts during mechanical substrate unfolding and translocation. Remarkably, we catch the proteasome in the act of unfolding the β-barrel mEos3.2 substrate while the ATPase hexamer is in a particular staircase register. Our findings advance current models for protein translocation through hexameric AAA+ motors and reveal how the proteasome uses its distinct conformational states to coordinate cofactor binding and substrate processing.

PubMed: 41198955
DOI: 10.1038/s41594-025-01695-2

実験手法

ELECTRON MICROSCOPY (3.04 Å)