7USE

Cryo-EM structure of WAVE regulatory complex with Rac1 bound on both A and D site

Summary for 7USE

• Entry DOI: 10.2210/pdb7use/pdb
• EMDB information: 26734
• Descriptor: Cytoplasmic FMR1-interacting protein 1, GUANOSINE-5'-TRIPHOSPHATE, Nck-associated protein 1, ... (10 entities in total)
• Functional Keywords: actin regulator, gtpase binding protein, cytoskeletal regulator, cell invasion
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 7
• Total formula weight: 381242.21

Authors

Ding, B.,Yang, S.,Chen, B.,Chowdhury, S. (deposition date: 2022-04-25, release date: 2022-09-21, Last modification date: 2024-06-12)

Primary citation

Ding, B.,Yang, S.,Schaks, M.,Liu, Y.,Brown, A.J.,Rottner, K.,Chowdhury, S.,Chen, B.
Structures reveal a key mechanism of WAVE regulatory complex activation by Rac1 GTPase.
Nat Commun, 13:5444-5444, 2022

PubMed Abstract: The Rho-family GTPase Rac1 activates the WAVE regulatory complex (WRC) to drive Arp2/3 complex-mediated actin polymerization in many essential processes. Rac1 binds to WRC at two distinct sites-the A and D sites. Precisely how Rac1 binds and how the binding triggers WRC activation remain unknown. Here we report WRC structures by itself, and when bound to single or double Rac1 molecules, at ~3 Å resolutions by cryogenic-electron microscopy. The structures reveal that Rac1 binds to the two sites by distinct mechanisms, and binding to the A site, but not the D site, drives WRC activation. Activation involves a series of unique conformational changes leading to the release of sequestered WCA (WH2-central-acidic) polypeptide, which stimulates the Arp2/3 complex to polymerize actin. Together with biochemical and cellular analyses, the structures provide a novel mechanistic understanding of how the Rac1-WRC-Arp2/3-actin signaling axis is regulated in diverse biological processes and diseases.

PubMed: 36114192
DOI: 10.1038/s41467-022-33174-3

Experimental method

ELECTRON MICROSCOPY (3 Å)