7MHS

Structure of p97 (subunits A to E) with substrate engaged

Summary for 7MHS

• Entry DOI: 10.2210/pdb7mhs/pdb
• EMDB information: 23835
• Descriptor: Transitional endoplasmic reticulum ATPase, Unknown substrate, ADENOSINE-5'-DIPHOSPHATE, ... (5 entities in total)
• Functional Keywords: p97, vcp, aaa+ atpase, peptide translocation, hydrolase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 6
• Total formula weight: 454068.93

Authors

Xu, Y.,Han, H.,Cooney, I.,Hill, C.P.,Shen, P.S. (deposition date: 2021-04-15, release date: 2022-05-11, Last modification date: 2024-05-29)

Primary citation

Xu, Y.,Han, H.,Cooney, I.,Guo, Y.,Moran, N.G.,Zuniga, N.R.,Price, J.C.,Hill, C.P.,Shen, P.S.
Active conformation of the p97-p47 unfoldase complex.
Nat Commun, 13:2640-2640, 2022

PubMed Abstract: The p97 AAA+ATPase is an essential and abundant regulator of protein homeostasis that plays a central role in unfolding ubiquitylated substrates. Here we report two cryo-EM structures of human p97 in complex with its p47 adaptor. One of the conformations is six-fold symmetric, corresponds to previously reported structures of p97, and lacks bound substrate. The other structure adopts a helical conformation, displays substrate running in an extended conformation through the pore of the p97 hexamer, and resembles structures reported for other AAA unfoldases. These findings support the model that p97 utilizes a "hand-over-hand" mechanism in which two residues of the substrate are translocated for hydrolysis of two ATPs, one in each of the two p97 AAA ATPase rings. Proteomics analysis supports the model that one p97 complex can bind multiple substrate adaptors or binding partners, and can process substrates with multiple types of ubiquitin modification.

PubMed: 35552390
DOI: 10.1038/s41467-022-30318-3

Experimental method

ELECTRON MICROSCOPY (3.6 Å)