Molecular mechanism of Arp2/3 complex inhibition by Arpin.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
02 02 2022
02 02 2022
Historique:
received:
27
10
2021
accepted:
09
01
2022
entrez:
3
2
2022
pubmed:
4
2
2022
medline:
16
2
2022
Statut:
epublish
Résumé
Positive feedback loops involving signaling and actin assembly factors mediate the formation and remodeling of branched actin networks in processes ranging from cell and organelle motility to mechanosensation. The Arp2/3 complex inhibitor Arpin controls the directional persistence of cell migration by interrupting a feedback loop involving Rac-WAVE-Arp2/3 complex, but Arpin's mechanism of inhibition is unknown. Here, we describe the cryo-EM structure of Arpin bound to Arp2/3 complex at 3.24-Å resolution. Unexpectedly, Arpin binds Arp2/3 complex similarly to WASP-family nucleation-promoting factors (NPFs) that activate the complex. However, whereas NPFs bind to two sites on Arp2/3 complex, on Arp2-ArpC1 and Arp3, Arpin only binds to the site on Arp3. Like NPFs, Arpin has a C-helix that binds at the barbed end of Arp3. Mutagenesis studies in vitro and in cells reveal how sequence differences within the C-helix define the molecular basis for inhibition by Arpin vs. activation by NPFs.
Identifiants
pubmed: 35110533
doi: 10.1038/s41467-022-28112-2
pii: 10.1038/s41467-022-28112-2
pmc: PMC8810855
doi:
Substances chimiques
Actin-Related Protein 2-3 Complex
0
Actins
0
Carrier Proteins
0
Cytoskeletal Proteins
0
arpin protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
628Subventions
Organisme : NCI NIH HHS
ID : HHSN261200800001E
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM073791
Pays : United States
Organisme : NIGMS NIH HHS
ID : RM1 GM136511
Pays : United States
Organisme : NIH HHS
ID : S10 OD023592
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM132039
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008275
Pays : United States
Informations de copyright
© 2022. The Author(s).
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