Why Does Synergistic Activation of WASP, but Not N-WASP, by Cdc42 and PIP₂ Require Cdc42 Prenylation?

ABSTRACT: Human WASP and N-WASP are homologous proteins that require the binding of multiple regulators, including the acidic lipid PIP₂ and the small GTPase Cdc42, to relieve autoinhibition before they can stimulate the initiation of actin polymerization. Autoinhibition involves intramolecular binding of the C-terminal acidic and central motifs to an upstream basic region and GTPase binding domain. Little is known about how a single intrinsically disordered protein, WASP or N-WASP, binds multiple regulators to achieve full activation. Here we used molecular dynamics simulations to characterize the binding of WASP and N-WASP with PIP₂ and Cdc42. In the absence of Cdc42, both WASP and N-WASP strongly associate with PIP₂-containing membranes, through their basic region

SUBMITTER: Dey S 

PROVIDER: S-EPMC10079582 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature