Clues to quality of journals
Open Access Policy of Helmholtz Association 2016
CC Licencences
Publication Metrics
Home
Deutsch
New EVA Application
Advanced Search
Browse by ...
Publication overview
Statistics (last 5 years)
OA Publications
Submit Publication
Import publication from...
Report missing publication
Contact persons
Help
Text
Endnote (RIS)
BibTeX
Publ. Version/Full Text
DOI
PMC
 |
Open Access Hybrid |
|
as soon as is submitted to ZB.
Characterizing ATP processing by the AAA+ protein p97 at the atomic level.
Nat. Chem. 16, 363-372 (2024)
The human enzyme p97 regulates various cellular pathways by unfolding hundreds of protein substrates in an ATP-dependent manner, making it an essential component of protein homeostasis and an impactful pharmacological target. The hexameric complex undergoes substantial conformational changes throughout its catalytic cycle. Here we elucidate the molecular motions that occur at the active site in the temporal window immediately before and after ATP hydrolysis by merging cryo-EM, NMR spectroscopy and molecular dynamics simulations. p97 populates a metastable reaction intermediate, the ADP·Pi state, which is poised between hydrolysis and product release. Detailed snapshots reveal that the active site is finely tuned to trap and eventually discharge the cleaved phosphate. Signalling pathways originating at the active site coordinate the action of the hexamer subunits and couple hydrolysis with allosteric conformational changes. Our multidisciplinary approach enables a glimpse into the sophisticated spatial and temporal orchestration of ATP handling by a prototype AAA+ protein.
Impact Factor
Scopus SNIP
Altmetric
19.200
0.000
Annotations
Special Publikation
Hide on homepage
Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Molecular-dynamics Simulations; Structural Basis; Cryo-em; Active-site; Hydrolysis; Mechanism; Software; Amber; Visualization; Parameters
Language
english
Publication Year
2024
HGF-reported in Year
2024
ISSN (print) / ISBN
1755-4330
e-ISSN
1755-4349
Journal
Nature chemistry
Quellenangaben
Volume: 16,
Issue: 3,
Pages: 363-372
Publisher
Nature Publishing Group
Publishing Place
London
Reviewing status
Peer reviewed
Institute(s)
Institute of Structural Biology (STB)
POF-Topic(s)
30203 - Molecular Targets and Therapies
Research field(s)
Enabling and Novel Technologies
PSP Element(s)
G-503000-001
Grants
German Research Foundation (DFG)
German Research Foundation (DFG)
WOS ID
001157664900002
Scopus ID
85184457241
PubMed ID
38326645
Erfassungsdatum
2024-04-19