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
Copyright policy )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
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 Gα(13) stimulates the guanine nucleotide exchange factor (GEF) activity of RH-RhoGEFs, leading to activation of RhoA. The mechanism by which Gα(13) stimulates the GEF activity of RH-RhoGEFs, such as p115RhoGEF, has not yet been fully elucidated. Here, specific residues in Gα(13) that mediate activation of p115RhoGEF are identified. Mutation of these residues significantly impairs binding of Gα(13) to p115RhoGEF as well as stimulation of GEF activity. These data suggest that the exchange activity of p115RhoGEF is stimulated allosterically by Gα(13) and not through its interaction with a secondary binding site. A crystal structure of Gα(13) bound to the RH domain of p115RhoGEF is also presented, which differs from a previously crystallized complex with a Gα(13)-Gα(i1) chimera. Taken together, these data provide new insight into the mechanism by which p115RhoGEF is activated by Gα(13).
- University of Chicago United States
- Advanced Science Research Center Japan
- University of Tokyo Japan
- Japan Atomic Energy Agency Japan
- University of Illinois System United States
Crystallography, X-Ray, GTP-Binding Protein alpha Subunits, G12-G13, Protein Structure, Tertiary, Enzyme Activation, Mice, Structure-Activity Relationship, Allosteric Regulation, Multienzyme Complexes, Mutation, Animals, Guanine Nucleotide Exchange Factors, Protein Structure, Quaternary, Rho Guanine Nucleotide Exchange Factors
Crystallography, X-Ray, GTP-Binding Protein alpha Subunits, G12-G13, Protein Structure, Tertiary, Enzyme Activation, Mice, Structure-Activity Relationship, Allosteric Regulation, Multienzyme Complexes, Mutation, Animals, Guanine Nucleotide Exchange Factors, Protein Structure, Quaternary, Rho Guanine Nucleotide Exchange Factors
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