7JPN

Cryo-EM structure of Arpin-bound Arp2/3 complex

Summary for 7JPN

• Entry DOI: 10.2210/pdb7jpn/pdb
• EMDB information: 22416
• Descriptor: Actin-related protein 3, ADENOSINE-5'-TRIPHOSPHATE, Actin-related protein 2, ... (10 entities in total)
• Functional Keywords: actin, atpase, actin related protein, arp, cytoskeleton, arp2-3 complex, actin nucleation, actin branching, contractile protein, arpin
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 8
• Total formula weight: 225823.59

Authors

van Eeuwen, T.,Fregoso, F.E.,Dominguez, R.,Zimmet, A.,Boczkowska, M.,Rebowski, G. (deposition date: 2020-08-09, release date: 2022-02-09, Last modification date: 2024-05-15)

Primary citation

Fregoso, F.E.,van Eeuwen, T.,Simanov, G.,Rebowski, G.,Boczkowska, M.,Zimmet, A.,Gautreau, A.M.,Dominguez, R.
Molecular mechanism of Arp2/3 complex inhibition by Arpin.
Nat Commun, 13:628-628, 2022

PubMed 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.

PubMed: 35110533
DOI: 10.1038/s41467-022-28112-2

Experimental method

ELECTRON MICROSCOPY (3.24 Å)