EMD-23449

Single-particle
3.09 Å
EMD-23449 Deposition: 06/02/2021
Map released: 15/09/2021
Last modified: 29/05/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-23449

Cryo-EM structure of human p97 in complex with Npl4/Ufd1 and polyubiquitinated Ub-Eos (CHAPSO, Class 1, Close State)

EMD-23449

Single-particle
3.09 Å
EMD-23449 Deposition: 06/02/2021
Map released: 15/09/2021
Last modified: 29/05/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens, Mus musculus
Sample: Human p97 in complex with Npl4/Ufd1 and K48-linked polyubiquitinated Ub-Eos in the presence of ATP
Fitted models: 7ln5 (Avg. Q-score: 0.415)

Deposition Authors: Pan M , Yu Y, Liu L , Zhao M
Mechanistic insight into substrate processing and allosteric inhibition of human p97.
Pan M , Yu Y, Ai H, Zheng Q, Xie Y , Liu L , Zhao M
(2021) Nat Struct Mol Biol , 28 , 614 - 625
PUBMED: 34262183
DOI: doi:10.1038/s41594-021-00617-2
ISSN: 1545-9985
Abstract:
p97 processes ubiquitinated substrates and plays a central role in cellular protein homeostasis. Here, we report a series of cryo-EM structures of the substrate-engaged human p97 complex with resolutions ranging from 2.9 to 3.8 Å that captured 'power-stroke'-like motions of both the D1 and D2 ATPase rings of p97. A key feature of these structures is the critical conformational changes of the intersubunit signaling (ISS) motifs, which tighten the binding of nucleotides and neighboring subunits and contribute to the spiral staircase conformation of the D1 and D2 rings. In addition, we determined the cryo-EM structure of human p97 in complex with NMS-873, a potent p97 inhibitor, at a resolution of 2.4 Å. The structures showed that NMS-873 binds at a cryptic groove in the D2 domain and interacts with the ISS motif, preventing its conformational change and thus blocking substrate translocation allosterically.