7LN3

Cryo-EM structure of human p97 in complex with Npl4/Ufd1 and polyubiquitinated Ub-Eos (FOM, Class 2)

7LN3 の概要

• エントリーDOI: 10.2210/pdb7ln3/pdb
• EMDBエントリー: 23442 23443 23444 23445 23446 23447 23448 23449 23450 23451 23452 23453 23454 23455 23456 23457 23458
• 分子名称: Transitional endoplasmic reticulum ATPase, polyubiquitinated Ub-Eos, ADENOSINE-5'-DIPHOSPHATE, ... (5 entities in total)
• 機能のキーワード: p97, nms-873, single-particle cryo-em, translocation, allosteric inhibition, translocase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 7
• 化学式量合計: 544709.84

構造登録者

Pan, M.,Yu, Y.,Liu, L.,Zhao, M. (登録日: 2021-02-06, 公開日: 2021-09-15, 最終更新日: 2024-05-29)

主引用文献

Pan, M.,Yu, Y.,Ai, H.,Zheng, Q.,Xie, Y.,Liu, L.,Zhao, M.
Mechanistic insight into substrate processing and allosteric inhibition of human p97.
Nat.Struct.Mol.Biol., 28:614-625, 2021

PubMed Abstract: p97 processes ubiquitinated substrates and plays a central role in cellular protein homeostasis. Here, we report a series of cryo-EM structures of the substrate-engaged human p97 complex with resolutions ranging from 2.9 to 3.8 Å that captured 'power-stroke'-like motions of both the D1 and D2 ATPase rings of p97. A key feature of these structures is the critical conformational changes of the intersubunit signaling (ISS) motifs, which tighten the binding of nucleotides and neighboring subunits and contribute to the spiral staircase conformation of the D1 and D2 rings. In addition, we determined the cryo-EM structure of human p97 in complex with NMS-873, a potent p97 inhibitor, at a resolution of 2.4 Å. The structures showed that NMS-873 binds at a cryptic groove in the D2 domain and interacts with the ISS motif, preventing its conformational change and thus blocking substrate translocation allosterically.

PubMed: 34262183
DOI: 10.1038/s41594-021-00617-2

実験手法

ELECTRON MICROSCOPY (3.45 Å)