7K57

Structure of apo VCP dodecamer generated from bacterially recombinant VCP/p97

Summary for 7K57

• Entry DOI: 10.2210/pdb7k57/pdb
• Related: 7K56
• EMDB information: 22675 22676
• Descriptor: Transitional endoplasmic reticulum ATPase (1 entity in total)
• Functional Keywords: aaa atpase, atp hydrolysis, segregase, cytosolic protein, hydrolase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 12
• Total formula weight: 1073577.94

Authors

Yu, G.,Bai, Y.,Li, K.,Jiang, W.,Zhang, Z.Y. (deposition date: 2020-09-16, release date: 2021-10-13, Last modification date: 2024-05-29)

Primary citation

Yu, G.,Bai, Y.,Li, K.,Amarasinghe, O.,Jiang, W.,Zhang, Z.Y.
Cryo-electron microscopy structures of VCP/p97 reveal a new mechanism of oligomerization regulation.
Iscience, 24:103310-103310, 2021

PubMed Abstract: VCP/p97 is an evolutionarily conserved AAA+ ATPase important for cellular homeostasis. Previous studies suggest that VCP predominantly exists as a homohexamer. Here, we performed structural and biochemical characterization of VCP dodecamer, an understudied state of VCP. The structure revealed an apo nucleotide status that has rarely been captured, a tail-to-tail assembly of two hexamers, and the up-elevated N-terminal domains akin to that seen in the ATP-bound hexamer. Further analyses elucidated a nucleotide status-dependent dodecamerization mechanism, where nucleotide dissociation from the D2 AAA domains induces and promotes VCP dodecamerization. In contrast, nucleotide-free D1 AAA domains are associated with the up-rotation of N-terminal domains, which may prime D1 for ATP binding. These results therefore reveal new nucleotide status-dictated intra- and interhexamer conformational changes and suggest that modulation of D2 domain nucleotide occupancy may serve as a mechanism in controlling VCP oligomeric states.

PubMed: 34765927
DOI: 10.1016/j.isci.2021.103310

Experimental method

ELECTRON MICROSCOPY (3.7 Å)