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| Title | Structural basis of VCP-VCPIP1-p47 ternary complex in Golgi maintenance. |
|---|---|
| Journal, issue, pages | Nat Commun, Vol. 16, Issue 1, Page 8025, Year 2025 |
| Publish date | Aug 28, 2025 |
Authors | Binita Shah / Moritz Hunkeler / Ariana Bratt / Hong Yue / Isabella Jaen Maisonet / Eric S Fischer / Sara J Buhrlage / ![]() |
| 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). ...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. |
External links | Nat Commun / PubMed:40877265 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 2.3 - 4.0 Å |
| Structure data | EMDB-48499, PDB-9mpq: EMDB-48500, PDB-9mpr: EMDB-48501, PDB-9mps: EMDB-48502, PDB-9mpt: ![]() EMDB-48503: Cryo-EM structure of VCP bound to VCPIP1 UBX and VCPID (with stalk region) ![]() EMDB-48504: Cryo-EM structure of VCP bound to p47 UBX domain and VCPIP1 VCPIDs (with stalk region) EMDB-48505, PDB-9mpu: EMDB-48506, PDB-9mpv: |
| Source |
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Keywords | HYDROLASE / double-ring hexameric complex / valosin containing protein / ATPase / VCP / mammalian / DUB / deubiquitinase / deubiquitinating enzyme / VCIP135 / p97 / VCPIP1 / VCPID / UBX / p47 / adapter / SHP |
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