9MQ6

Cryo-EM structure of VCP/p97 and VCPIP1 (VCIP135) in the presence of AMPPNP

9MQ6 の概要

• エントリーDOI: 10.2210/pdb9mq6/pdb
• 関連するPDBエントリー: 9DIL
• EMDBエントリー: 48514
• 分子名称: Transitional endoplasmic reticulum ATPase, Deubiquitinating protein VCPIP1, ADENOSINE-5'-DIPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: atpase, unfoldase, deubiquitinase, hydrolase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 315242.92

構造登録者

Vostal, L.E.,Kapoor, T.M. (登録日: 2025-01-02, 公開日: 2025-03-26, 最終更新日: 2025-05-21)

主引用文献

Vostal, L.E.,Dahan, N.E.,Reynolds, M.J.,Kronenberg, L.I.,Kapoor, T.M.
Structural insights into the coupling between VCP, an essential unfoldase, and a deubiquitinase.
J.Cell Biol., 224:-, 2025

PubMed Abstract: Proteostasis involves degradation and recycling of proteins from organelles, membranes, and multiprotein complexes. These processes can depend on protein extraction and unfolding by the essential mechanoenzyme valosin-containing protein (VCP) and on ubiquitin chain remodeling by ubiquitin-specific proteases known as deubiquitinases (DUBs). How the activities of VCP and DUBs are coordinated is poorly understood. Here, we focus on the DUB VCPIP1, a VCP interactor required for post-mitotic Golgi and ER organization. We determine ∼3.3 Å cryogenic electron microscopy structures of VCP-VCPIP1 complexes in the absence of added nucleotide or the presence of an ATP analog. We find that up to 3 VCPIP1 protomers interact with the VCP hexamer to position VCPIP1's catalytic domain at the exit of VCP's central pore, poised to cleave ubiquitin following substrate unfolding. We observe competition between VCPIP1 and other cofactors for VCP binding and show that VCP stimulates VCPIP1's DUB activity. Together, our data suggest how the two enzyme activities can be coordinated to regulate proteostasis.

PubMed: 40085114
DOI: 10.1083/jcb.202410148

実験手法

ELECTRON MICROSCOPY (3.3 Å)