Stabilization of Interdomain Interactions in G protein α_i Subunits Determines 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 the functional properties of these proteins with respect to GDP/GTP binding and regulation of adenylate cyclase are very similar. We recently identified PDZ-RhoGEF (PRG) as a novel Gα_i1 effector, however, it is poorly activated by Gα_i2. Here, 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

SUBMITTER: Lefevre TJ 

PROVIDER: S-EPMC10103935 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature