3P8C

Structure and Control of the Actin Regulatory WAVE Complex

Summary for 3P8C

• Entry DOI: 10.2210/pdb3p8c/pdb
• Descriptor: Cytoplasmic FMR1-interacting protein 1, Nck-associated protein 1, Wiskott-Aldrich syndrome protein family member 1, ... (9 entities in total)
• Functional Keywords: actin polymerization, protein binding
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm : Q7L576; Cell membrane ; Single-pass membrane protein ; Cytoplasmic side : Q9Y2A7; Cytoplasm, cytoskeleton : Q92558 Q8WUW1
• Total number of polymer chains: 5
• Total formula weight: 333843.42

Authors

Chen, Z.,Borek, D.,Padrick, S.B.,Gomez, T.S.,Metlagel, Z.,Ismail, A.M.,Umetani, J.,Billadeau, D.D.,Otwinowski, Z.,Rosen, M.K. (deposition date: 2010-10-13, release date: 2010-12-01, Last modification date: 2024-02-21)

Primary citation

Chen, Z.,Borek, D.,Padrick, S.B.,Gomez, T.S.,Metlagel, Z.,Ismail, A.M.,Umetani, J.,Billadeau, D.D.,Otwinowski, Z.,Rosen, M.K.
Structure and control of the actin regulatory WAVE complex.
Nature, 468:533-538, 2010

PubMed 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.

PubMed: 21107423
DOI: 10.1038/nature09623

Experimental method

X-RAY DIFFRACTION (2.29 Å)