Journal article
Structure and control of the actin regulatory WAVE complex
Nature (London), v 468(7323), pp 533-538
25 Nov 2010
PMID: 21107423
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Members of the Wiskott-Aldrich syndrome protein (WASP) family control cytoskeletal dynamics by promoting actin filament nucleation with the Arp2/3 complex. The WASP relative WAVE regulates lamellipodia formation within a 400-kilodalton, hetero-pentameric WAVE regulatory complex (WRC). The WRC is inactive towards the Arp2/3 complex, but can be stimulated by the Rac GTPase, kinases and phosphatidylinositols. Here we report the 2.3-ångstrom crystal structure of the WRC and complementary mechanistic analyses. The structure shows that the activity-bearing VCA motif of WAVE is sequestered by a combination of intramolecular and intermolecular contacts within the WRC. Rac and kinases appear to destabilize a WRC element that is necessary for VCA sequestration, suggesting the way in which these signals stimulate WRC activity towards the Arp2/3 complex. The spatial proximity of the Rac binding site and the large basic surface of the WRC suggests how the GTPase and phospholipids could cooperatively recruit the complex to membranes.
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Details
- Title
- Structure and control of the actin regulatory WAVE complex
- Creators
- Zhucheng Chen - The University of Texas Southwestern Medical CenterDominika BorekShae B PadrickTimothy S GomezZoltan MetlagelAyman M IsmailJunko UmetaniDaniel D BilladeauZbyszek OtwinowskiMichael K Rosen
- Publication Details
- Nature (London), v 468(7323), pp 533-538
- Publisher
- Springer Nature
- Grant note
- R01-GM053163 / NIGMS NIH HHS R01 GM053163 / NIGMS NIH HHS T32 AI007047 / NIAID NIH HHS R01-AI065474 / NIAID NIH HHS R01-GM056322 / NIGMS NIH HHS Howard Hughes Medical Institute 1F32-GM06917902 / NIGMS NIH HHS R01 GM056322-15 / NIGMS NIH HHS R01 AI065474 / NIAID NIH HHS AI07047 / NIAID NIH HHS R01 GM056322 / NIGMS NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000284584200035
- Scopus ID
- 2-s2.0-78649452812
- Other Identifier
- 991020836453904721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology