| Autor: |
Chen, Zhucheng, Borek, Dominika, Padrick, Shae B., Gomez, Timothy S., Metlagel, Zoltan, Ismail, Ayman M., Umetani, Junko, Billadeau, Daniel D., Otwinowski, Zbyszek, Rosen, Michael K. |
| Zdroj: |
ETSU Faculty Works. |
| Druh dokumentu: |
Text |
| DOI: |
10.1038/nature09623 |
| Popis: |
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-ngstrom 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. |
| Databáze: |
Networked Digital Library of Theses & Dissertations |
| Externí odkaz: |
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