Interaction of human retinal RGS with G-protein alpha-subunits.

A novel family of RGS proteins negatively regulates signaling via heterotrimeric G-proteins by accelerating the GTPase activity of G-protein alpha subunits. We have investigated interaction of human retinal RGS protein (hRGSr) with in vitro translated G(alpha) subunits: G(t alpha), G(i alpha1), G(o alpha) and G(s alpha). hRGSr binds well to G(t alpha), G(i alpha1) and G(o alpha) in the presence of AIF4-, but does not interact with G(s alpha). The N- and C-terminally truncated G(alpha) subunits interact with hRGSr similarly to the intact G(alpha) polypeptides. Analysis of interaction between hRGSr and G(o alpha)/G(s alpha) chimeras suggests that a region of G(o alpha), G(o alpha)22-212, contains major structural determinants for binding to RGS proteins.