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Structural analysis of the transitional state of Arp2/3 complex activation by two actin-bound WCAs.

ABSTRACT: Actin filament nucleation and branching by Arp2/3 complex is activated by nucleation-promoting factors (NPFs), whose C-terminal WCA region contains binding sites for actin (W) and Arp2/3 complex (CA). It is debated whether one or two NPFs are required for activation. Here we present evidence in support of the two-NPF model and show that actin plays a crucial role in the interactions of two mammalian NPFs, N-WASP and WAVE2, with Arp2/3 complex. Competition between actin-WCA and glia maturation factor (GMF) for binding to Arp2/3 complex suggests that during activation the first actin monomer binds at the barbed end of Arp2. Based on distance constraints obtained by time-resolved fluorescence resonance energy transfer, we define the relative position of the two actin-WCAs on Arp2/3 complex and propose an atomic model of the 11-subunit transitional complex.

SUBMITTER: Boczkowska M

PROVIDER: S-EPMC4364448 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Structural analysis of the transitional state of Arp2/3 complex activation by two actin-bound WCAs.

Boczkowska Malgorzata M Rebowski Grzegorz G Kast David J DJ Dominguez Roberto R

Nature communications 20140101

Actin filament nucleation and branching by Arp2/3 complex is activated by nucleation-promoting factors (NPFs), whose C-terminal WCA region contains binding sites for actin (W) and Arp2/3 complex (CA). It is debated whether one or two NPFs are required for activation. Here we present evidence in support of the two-NPF model and show that actin plays a crucial role in the interactions of two mammalian NPFs, N-WASP and WAVE2, with Arp2/3 complex. Competition between actin-WCA and glia maturation fa ...[more]

PMID: 24518936

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