Fidelity of G protein beta-subunit association by the G protein gamma-subunit-like domains of RGS6, RGS7, and RGS11.
Several regulators of G protein signaling (RGS) proteins contain a G protein gamma-subunit-like (GGL) domain, which, as we have shown, binds to Gbeta5 subunits. Here, we extend our original findings by describing another GGL-domain-containing RGS, human RGS6. When RGS6 is coexpressed with different Gbeta subunits, only RGS6 and Gbeta5 interact. The expression of mRNA for RGS6 and Gbeta5 in human tissues overlaps. Predictions of alpha-helical and coiled-coil character within GGL domains, coupled with measurements of Gbeta binding by GGL domain mutants, support the contention that Ggamma-like regions within RGS proteins interact with Gbeta5 subunits in a fashion comparable to conventional Gbeta/Ggamma pairings. Mutation of the highly conserved Phe-61 residue of Ggamma2 to tryptophan, the residue present in all GGL domains, increases the stability of the Gbeta5/Ggamma2 heterodimer, highlighting the importance of this residue to GGL/Gbeta5 association.
Snow
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BE
Amgen Institute, Toronto, ON, Canada M5G2C1.
Betts
L
L
Mangion
J
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Sondek
J
J
Siderovski
D P
DP
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D018076:DNA, Complementary; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D046911:Macromolecular Substances; D008958:Models, Molecular; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020710:RGS Proteins; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D014162:Transfection
D018076:DNA, Complementary; D046911:Macromolecular Substances; D011506:Proteins; D020710:RGS Proteins; C492039:RGS7 protein, human; D012333:RNA, Messenger; D011994:Recombinant Proteins; D019204:GTP-Binding Proteins