Structure of the rgRGS domain of p115RhoGEF

p115RhoGEF, a guanine nucleotide exchange factor for Rho GTPase, is also a GTPase activating protein (GAP) for G(12) and G(13) heterotrimeric G alpha subunits. Near its N-terminus, p115RhoGEF contains a domain (rgRGS) with re mote sequence identity to RGS (regulators of G protein signaling) domains. The rgRGS domain is necessary but not sufficient for the GAP activity of p1 15RhoGEF. The 1.9 Angstrom resolution crystal structure of the rgRGS domain shows structural similarity to RGS domains but possesses a C-terminal exte nsion that folds into a layer of helices that pack against the hydrophobic core of the domain. Mutagenesis experiments show that rgRGS may form intera ctions with G alpha (13) that are analogous to those in complexes of RGS pr oteins with their G alpha substrates.