Structural basis for allosteric regulation of human phosphofructokinase-1.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
25 Aug 2024
25 Aug 2024
Historique:
received:
28
03
2024
accepted:
19
08
2024
medline:
26
8
2024
pubmed:
26
8
2024
entrez:
25
8
2024
Statut:
epublish
Résumé
Phosphofructokinase-1 (PFK1) catalyzes the rate-limiting step of glycolysis, committing glucose to conversion into cellular energy. PFK1 is highly regulated to respond to the changing energy needs of the cell. In bacteria, the structural basis of PFK1 regulation is a textbook example of allostery; molecular signals of low and high cellular energy promote transition between an active R-state and inactive T-state conformation, respectively. Little is known, however, about the structural basis for regulation of eukaryotic PFK1. Here, we determine structures of the human liver isoform of PFK1 (PFKL) in the R- and T-state by cryoEM, providing insight into eukaryotic PFK1 allosteric regulatory mechanisms. The T-state structure reveals conformational differences between the bacterial and eukaryotic enzyme, the mechanisms of allosteric inhibition by ATP binding at multiple sites, and an autoinhibitory role of the C-terminus in stabilizing the T-state. We also determine structures of PFKL filaments that define the mechanism of higher-order assembly and demonstrate that these structures are necessary for higher-order assembly of PFKL in cells.
Identifiants
pubmed: 39183237
doi: 10.1038/s41467-024-51808-6
pii: 10.1038/s41467-024-51808-6
doi:
Substances chimiques
Phosphofructokinase-1
EC 2.7.1.11
Adenosine Triphosphate
8L70Q75FXE
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
7323Subventions
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)
ID : P20GM144230
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)
ID : 1R35GM149542
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)
ID : S10OD023476
Informations de copyright
© 2024. The Author(s).
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