8YKA

Cryo-EM structure of P97-VCPIP1 complex

Summary for 8YKA

• Entry DOI: 10.2210/pdb8yka/pdb
• EMDB information: 39360
• Descriptor: Transitional endoplasmic reticulum ATPase, Deubiquitinating protein VCPIP1 (2 entities in total)
• Functional Keywords: p97/vcp atpase; golgi apparatus; membrane fusion; vcpip1, hydrolase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 9
• Total formula weight: 703423.33

Authors

Liu, Y.,Lu, P.,Gao, H.,Li, F. (deposition date: 2024-03-04, release date: 2024-10-02, Last modification date: 2024-11-20)

Primary citation

Liao, T.,Li, R.,Lu, P.,Liu, Y.,Yang, R.,Guo, H.,Wu, Z.,Wang, R.,Yuan, L.,Hu, Z.,Gao, H.,Li, F.
Molecular Basis of VCPIP1 and P97/VCP Interaction Reveals Its Functions in Post-Mitotic Golgi Reassembly.
Adv Sci, 11:e2403417-e2403417, 2024

PubMed Abstract: The VCPIP1-P97/VCP (Valosin-Containing Protein) complex is required for post-mitotic Golgi cisternae reassembly and maintenance in interphase. However, the organization and mechanism of this complex in regulating Golgi membrane fusion is still elusive. Here, the cryo-electron microscopy (cryo-EM) structures of the human VCPIP1-P97/VCP complex are presented. These studies reveal that three independent VCPIP1 molecules sit over the C-terminal substrate exit tunnel formed by P97/VCP homo-hexamer, resulting in an unusual C3 to C6 symmetric barrel architecture. The UFD1 (unknown function domain 1) from VCPIP1, but not the N-terminal OTU domain and the C-terminal UBL domain, docks to the two adjacent D2 domains of P97/VCP, allosterically causing the cofactors binding domain-NTDs (N-terminal domains) of P97/VCP in a "UP" and D1 domain in an ATPase competent conformation. Conversely, VCPIP1 bound P97/VCP hexamer favors the binding of P47, and thus the intact SNARE complex, promoting Golgi membrane fusion. These studies not only reveal the unexpected organization of humanVCPIP1-P97/VCP complex, but also provide new insights into the mechanism of VCPIP1-P97/VCP mediated Golgi apparatus reassembly, which is a fundamental cellular event for protein and lipid processing.

PubMed: 39234822
DOI: 10.1002/advs.202403417

Experimental method

ELECTRON MICROSCOPY (3.45 Å)