7use | pdb_00007use

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

spinqualitylabelsall models 7use, resolution 3.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7use is a 7 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3Å Ligands: GNP, GTP, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 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 A 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. Structures reveal a key mechanism of WAVE regulatory complex activation by Rac1 GTPase.,Ding B, Yang S, Schaks M, Liu Y, Brown AJ, Rottner K, Chowdhury S, Chen B Nat Commun. 2022 Sep 16;13(1):5444. doi: 10.1038/s41467-022-33174-3. PMID:36114192 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Rac 3D structures Wiskott-Aldrich syndrome protein 3D structures

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