5KIY

p97 ND1-A232E in complex with VIMP

Summary for 5KIY

• Entry DOI: 10.2210/pdb5kiy/pdb
• Related: 5KIW
• Descriptor: Transitional endoplasmic reticulum ATPase, Selenoprotein S, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ... (5 entities in total)
• Functional Keywords: p97 adaptor protein, vcp-interacting membrane protein, vimp, hydrolase-membrane protein complex, hydrolase/membrane protein
• Biological source: Homo sapiens (Human); More
• Cellular location: Cytoplasm, cytosol : P55072; Endoplasmic reticulum membrane; Single-pass membrane protein: Q9BQE4
• Total number of polymer chains: 2
• Total formula weight: 62633.65

Authors

Tang, W.K.,Xia, D. (deposition date: 2016-06-17, release date: 2017-12-20, Last modification date: 2023-09-27)

Primary citation

Tang, W.K.,Zhang, T.,Ye, Y.,Xia, D.
Structural basis for nucleotide-modulated p97 association with the ER membrane.
Cell Discov, 3:17045-17045, 2017

PubMed Abstract: Association of the cytosolic AAA (ATPases associated with various cellular activities) protein p97 to membranes is essential for various cellular processes including endoplasmic reticulum (ER)-associated degradation. The p97 consists of two ATPase domains and an N domain that interacts with numerous cofactors. The N domain of p97 is known to undergo a large nucleotide-dependent conformation switch, but its physiological relevance is unclear. Here we show p97 is recruited to canine ER membranes predominantly by interacting with VCP-interacting membrane protein (VIMP), an ER-resident protein. We found that the recruitment is modulated through a nucleotide-dependent conformation switch of the N domain in wild-type p97, but this modulation is absent in pathogenic mutants. We demonstrate the molecular mechanism of the modulation by a series of structures of p97, VIMP and their complexes and suggest a physiological role of the nucleotide-dependent N domain conformation switch. The lack of modulation in pathogenic mutants is caused by changes in interactions between the N and D1 domain, as demonstrated by multiple intermediate positions adopted by N domains of mutant p97. Our findings suggest the nucleotide-modulated membrane association may also have a role in other p97-dependent processes.

PubMed: 29238611
DOI: 10.1038/celldisc.2017.45

Experimental method

X-RAY DIFFRACTION (2.79 Å)