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Arp2/3 complex is bound and activated by two WASP proteins.

ABSTRACT: Actin related protein 2/actin related protein 3 (Arp2/3) complex nucleates new actin filaments in eukaryotic cells in response to signals from proteins in the Wiskott-Aldrich syndrome protein (WASP) family. The conserved VCA domain of WASP proteins activates Arp2/3 complex by inducing conformational changes and delivering the first actin monomer of the daughter filament. Previous models of activation have invoked a single VCA acting at a single site on Arp2/3 complex. Here we show that activation most likely involves engagement of two distinct sites on Arp2/3 complex by two VCA molecules, each delivering an actin monomer. One site is on Arp3 and the second is on ARPC1 and Arp2. The VCAs at these sites have distinct roles in activation. Our findings reconcile apparently conflicting literature on VCA activation of Arp2/3 complex and lead to a new model for this process.

SUBMITTER: Padrick SB

PROVIDER: S-EPMC3158169 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Arp2/3 complex is bound and activated by two WASP proteins.

Padrick Shae B SB Doolittle Lynda K LK Brautigam Chad A CA King David S DS Rosen Michael K MK

Proceedings of the National Academy of Sciences of the United States of America 20110615 33

Actin related protein 2/actin related protein 3 (Arp2/3) complex nucleates new actin filaments in eukaryotic cells in response to signals from proteins in the Wiskott-Aldrich syndrome protein (WASP) family. The conserved VCA domain of WASP proteins activates Arp2/3 complex by inducing conformational changes and delivering the first actin monomer of the daughter filament. Previous models of activation have invoked a single VCA acting at a single site on Arp2/3 complex. Here we show that activatio ...[more]

PMID: 21676863

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