The two p190RhoGAP proteins, p190RhoGAP-A and-B, are key regulators of Rho GTPase
signaling and are essential for actin cytoskeletal structure and contractility. Here we report
the discovery of two evolutionarily conserved GTPase-like domains located in the 'middle
domain', previously thought to be unstructured. Deletion of these domains reduces RhoGAP
activity. Crystal structures, MANT-GTPγS binding, thermal denaturation, biochemical assays
and sequence homology analysis all strongly support defects in nucleotide-binding activity …