The nucleotide switch in Cdc42 modulates coupling between the GTPase-binding and allosteric equilibria of Wiskott-Aldrich syndrome protein.

ABSTRACT: The GTP/GDP nucleotide switch in Ras superfamily GTPases generally involves differential affinity toward downstream effectors, with the GTP-bound state having a higher affinity for effector than the GDP-bound state. We have developed a quantitative model of allosteric regulation of the Wiskott-Aldrich syndrome protein (WASP) by the Rho GTPase Cdc42 to better understand how GTPase binding is coupled to effector activation. The model accurately predicts WASP affinity for Cdc42, activity toward Arp2/3 complex, and activation by Cdc42 as functions of a two-state allosteric equilibrium in WASP. The ratio of GTPase affinities for the inactive and active states of WASP is appreciably larger for Cdc42-GTP than for Cdc42-GDP. The greater ability to distinguish between the two states of WASP makes C

SUBMITTER: Leung DW 

PROVIDER: S-EPMC556282 | biostudies-literature | 2005 Apr

REPOSITORIES: biostudies-literature