Stabilization of interdomain interactions in G protein α subunits as a determinant of Gα_i subtype signaling specificity.

ABSTRACT: Highly homologous members of the Gα_i family, Gα_i1-3, have distinct tissue distributions and physiological functions, yet their biochemical and functional properties are very similar. We recently identified PDZ-RhoGEF (PRG) as a novel Gα_i1 effector that is poorly activated by Gα_i2. In a proteomic proximity labeling screen we observed a strong preference for Gα_i1 relative to Gα_i2 with respect to engagement of a broad range of potential targets. We investigated the mechanistic basis for this selectivity using PRG as a representative target. Substitution of either the helical domain (HD) from Gα_i1 into Gα_i2 or substitution of a single amino acid, A230 in Gα_i2 with the corresponding D in Gα_i1

SUBMITTER: Lefevre TJ 

PROVIDER: S-EPMC11066577 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature