Myr-Arf1 conformational flexibility at the membrane surface sheds light on the interactions with ArfGAP ASAP1.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
21 Nov 2023
21 Nov 2023
Historique:
received:
12
05
2023
accepted:
30
10
2023
medline:
27
11
2023
pubmed:
22
11
2023
entrez:
21
11
2023
Statut:
epublish
Résumé
ADP-ribosylation factor 1 (Arf1) interacts with multiple cellular partners and membranes to regulate intracellular traffic, organelle structure and actin dynamics. Defining the dynamic conformational landscape of Arf1 in its active form, when bound to the membrane, is of high functional relevance and key to understanding how Arf1 can alter diverse cellular processes. Through concerted application of nuclear magnetic resonance (NMR), neutron reflectometry (NR) and molecular dynamics (MD) simulations, we show that, while Arf1 is anchored to the membrane through its N-terminal myristoylated amphipathic helix, the G domain explores a large conformational space, existing in a dynamic equilibrium between membrane-associated and membrane-distal conformations. These configurational dynamics expose different interfaces for interaction with effectors. Interaction with the Pleckstrin homology domain of ASAP1, an Arf-GTPase activating protein (ArfGAP), restricts motions of the G domain to lock it in what seems to be a conformation exposing functionally relevant regions.
Identifiants
pubmed: 37989735
doi: 10.1038/s41467-023-43008-5
pii: 10.1038/s41467-023-43008-5
pmc: PMC10663523
doi:
Substances chimiques
ADP-Ribosylation Factor 1
EC 3.6.5.2
ADP-Ribosylation Factors
EC 3.6.5.2
GTPase-Activating Proteins
0
Actins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
7570Subventions
Organisme : NIGMS NIH HHS
ID : P41 GM104601
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM123455
Pays : United States
Organisme : Intramural NIH HHS
ID : Z01 BC007365
Pays : United States
Informations de copyright
© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
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