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Identification of Critical Residues in Gα13 for Stimulation of p115RhoGEF Activity and the Structure of the Gα13-p115RhoGEF Regulator of G Protein Signaling Homology (RH) Domain Complex*

By Nicole Hajicek, Mutsuko Kukimoto-Niino, Chiemi Mishima-Tsumagari, Christina R. Chow, Mikako Shirouzu, Takaho Terada, Maulik Patel, Shigeyuki Yokoyama and Tohru Kozasa

Abstract

RH-RhoGEFs are a family of guanine nucleotide exchange factors that contain a regulator of G protein signaling homology (RH) domain. The heterotrimeric G protein Gα13 stimulates the guanine nucleotide exchange factor (GEF) activity of RH-RhoGEFs, leading to activation of RhoA. The mechanism by which Gα13 stimulates the GEF activity of RH-RhoGEFs, such as p115RhoGEF, has not yet been fully elucidated. Here, specific residues in Gα13 that mediate activation of p115RhoGEF are identified. Mutation of these residues significantly impairs binding of Gα13 to p115RhoGEF as well as stimulation of GEF activity. These data suggest that the exchange activity of p115RhoGEF is stimulated allosterically by Gα13 and not through its interaction with a secondary binding site. A crystal structure of Gα13 bound to the RH domain of p115RhoGEF is also presented, which differs from a previously crystallized complex with a Gα13-Gαi1 chimera. Taken together, these data provide new insight into the mechanism by which p115RhoGEF is activated by Gα13

Topics: Signal Transduction
Publisher: American Society for Biochemistry and Molecular Biology
OAI identifier: oai:pubmedcentral.nih.gov:3121507
Provided by: PubMed Central
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