Molecular mechanism of Arp2/3 complex inhibition by Arpin

Fred E. Fregoso, Trevor Eeuwen, Gleb Simanov, Grzegorz Rebowski, Malgorzata Boczkowska, Austin Zimmet, Alexis M. Gautreau and Roberto Dominguez ()
Additional contact information
Fred E. Fregoso: University of Pennsylvania
Trevor Eeuwen: University of Pennsylvania
Gleb Simanov: Laboratoire de Biologie Structurale de la Cellule, CNRS, Institut Polytechnique de Paris
Grzegorz Rebowski: University of Pennsylvania
Malgorzata Boczkowska: University of Pennsylvania
Austin Zimmet: University of Pennsylvania
Alexis M. Gautreau: Laboratoire de Biologie Structurale de la Cellule, CNRS, Institut Polytechnique de Paris
Roberto Dominguez: University of Pennsylvania

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: Abstract 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.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (3)

Downloads: (external link)
https://www.nature.com/articles/s41467-022-28112-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28112-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-28112-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().