Structural domains and components of active and inactive WAVE regulatory complex (WRC). The multi-protein complex WRC is a stable heterocomplex consisting of HSPC300, wave homology domain (WHD), Abl interactor 1/2/3 (Abi1/2/3), NCK associated protein 1 (NckAP1/Hem1), specifically Rac1-associated protein 1 (Sra1/PIR121). WAVE2 is autoinhibited in a basal state through the interaction between the complex proteins and the VCA region. Upon certain phosphorylation signals the closed complex is released into an open and active WRC which is then translocated to the cell membrane via interactions with the phosphatidylinositol-(3,4,5)-triphosphate (PIP3) and insulin receptor substrate of 53 kDa (IRSp53). The binding of Rho family of GTPases (GTP-Rac) increases the affinity of WAVE2 for IRSp53. This IRSp53 promotes the ability of WAVE2 to stimulate actin-related protein 2/3 complex (Arp2/3)-mediated actin polymerization.