9MPR

Cryo-EM structure of three VCPIP1 VCPIDs bound to VCP

Summary for 9MPR

• Entry DOI: 10.2210/pdb9mpr/pdb
• EMDB information: 48500
• Descriptor: Deubiquitinating protein VCPIP1, Transitional endoplasmic reticulum ATPase (2 entities in total)
• Functional Keywords: double-ring hexameric complex, valosin containing protein, atpase, vcp, mammalian, dub, deubiquitinase, deubiquitinating enzyme, vcip135, p97, vcpip1, hydrolase, vcpid
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 9
• Total formula weight: 964141.50

Authors

Shah, B.,Hunkeler, M.,Buhrlage, S.J.,Fischer, E.S. (deposition date: 2024-12-31, release date: 2025-10-15)

Primary citation

Shah, B.,Hunkeler, M.,Bratt, A.,Yue, H.,Jaen Maisonet, I.,Fischer, E.S.,Buhrlage, S.J.
Structural basis of VCP-VCPIP1-p47 ternary complex in Golgi maintenance.
Nat Commun, 16:8025-8025, 2025

PubMed Abstract: VCP/p97 regulates a wide range of cellular processes, including post-mitotic Golgi reassembly. In this context, VCP is assisted by p47, an adapter protein, and VCPIP1, a deubiquitylase (DUB). However, how they organize into a functional ternary complex to promote Golgi assembly remains unknown. Here, we use cryo-EM to characterize both VCP-VCPIP1 and VCP-VCPIP1-p47 complexes. We show that VCPIP1 engages VCP through two interfaces: one involving the N-domain of VCP and the UBX domain of VCPIP1, and the other involving the VCP D2 domains and a region of VCPIP1 we refer to as VCPID. The p47 UBX domain competitively binds to the VCP N-domain, while not affecting VCPID binding. We show that VCPID is critical for VCP-mediated enhancement of DUB activity and proper Golgi assembly. The ternary structure along with biochemical and cellular data provides new insights into the complex interplay of VCP with its co-factors.

PubMed: 40877265
DOI: 10.1038/s41467-025-63161-3

Experimental method

ELECTRON MICROSCOPY (2.9 Å)