8PQX

p97 (VCP) mutant - F539A state III

8PQX の概要

• エントリーDOI: 10.2210/pdb8pqx/pdb
• EMDBエントリー: 17827
• 分子名称: Transitional endoplasmic reticulum ATPase, ADENOSINE-5'-TRIPHOSPHATE, ADENOSINE-5'-DIPHOSPHATE (3 entities in total)
• 機能のキーワード: hexameric complex, atpase, unfoldase, protein quality control, segregase, chaperone
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 541370.75

構造登録者

Arie, M.,Matzov, D.,Karmona, R.,Szenkier, N.,Stanhill, A.,Navon, A. (登録日: 2023-07-12, 公開日: 2024-05-29, 最終更新日: 2024-12-25)

主引用文献

Arie, M.,Matzov, D.,Karmona, R.,Szenkier, N.,Stanhill, A.,Navon, A.
A non-symmetrical p97 conformation initiates a multistep recruitment of Ufd1/Npl4.
Iscience, 27:110061-110061, 2024

PubMed Abstract: experiments and cryo-EM structures of p97 and its cofactor, Ufd1/Npl4 (UN), elucidated substrate processing. Yet, the structural transitions and the related ATPase cycle upon UN binding remain unresolved. We captured two discrete conformations: One in which D1 protomers are ATP bound, while the D2 subunits are in the ADP state, presumably required for substrate engagement with the D2 pore; and a heterologous nucleotide state within the D1 ring in which only two NTDs are in the "up" ATP state that favors UN binding. Further analysis suggests that initially, UN binds p97's non-symmetrical conformation, this association promotes a structural transition upon which five NTDs shift to an "up" state and are poised to bind ATP. The UBXL domain of Npl4 was captured bound to an NTD in the ADP state, demonstrating a conformation that may provide directionality to incoming substrate and introduce the flexibility needed for substrate processing.

PubMed: 38947518
DOI: 10.1016/j.isci.2024.110061

実験手法

ELECTRON MICROSCOPY (3.3 Å)