Visualization of the Cdc48 AAA+ ATPase protein unfolding pathway.
Valosin Containing Protein
/ metabolism
Saccharomyces cerevisiae Proteins
/ metabolism
Saccharomyces cerevisiae
Protein Unfolding
Adenosine Triphosphate
/ metabolism
Cell Cycle Proteins
/ metabolism
Adenosine Triphosphatases
/ metabolism
Models, Molecular
Protein Binding
Hydrolysis
Intracellular Signaling Peptides and Proteins
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
29 Aug 2024
29 Aug 2024
Historique:
received:
20
12
2023
accepted:
20
08
2024
medline:
1
9
2024
pubmed:
1
9
2024
entrez:
29
8
2024
Statut:
epublish
Résumé
The Cdc48 AAA+ ATPase is an abundant and essential enzyme that unfolds substrates in multiple protein quality control pathways. The enzyme includes two conserved AAA+ ATPase motor domains, D1 and D2, that assemble as hexameric rings with D1 stacked above D2. Here, we report an ensemble of native structures of Cdc48 affinity purified from budding yeast lysate in complex with the adaptor Shp1 in the act of unfolding substrate. Our analysis reveals a continuum of structural snapshots that spans the entire translocation cycle. These data uncover elements of Shp1-Cdc48 interactions and support a 'hand-over-hand' mechanism in which the sequential movement of individual subunits is closely coordinated. D1 hydrolyzes ATP and disengages from substrate prior to D2, while D2 rebinds ATP and re-engages with substrate prior to D1, thereby explaining the dominant role played by the D2 motor in substrate translocation/unfolding.
Identifiants
pubmed: 39209885
doi: 10.1038/s41467-024-51835-3
pii: 10.1038/s41467-024-51835-3
pmc: PMC11362554
doi:
Substances chimiques
Valosin Containing Protein
EC 3.6.4.6
Saccharomyces cerevisiae Proteins
0
CDC48 protein, S cerevisiae
EC 3.6.4.-
SHP1 protein, S cerevisiae
0
Adenosine Triphosphate
8L70Q75FXE
Cell Cycle Proteins
0
Adenosine Triphosphatases
EC 3.6.1.-
Intracellular Signaling Peptides and Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
7505Subventions
Organisme : NIA NIH HHS
ID : R01 AG066874
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM112080
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM133772
Pays : United States
Organisme : NCI NIH HHS
ID : F31 CA254427
Pays : United States
Organisme : NIAID NIH HHS
ID : U54 AI170856
Pays : United States
Informations de copyright
© 2024. The Author(s).
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