Active G alpha (i)–i1/i2/i3 binds RGS proteins

Stable Identifier
Reaction [binding]
Homo sapiens
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G Protein Coupled Receptors (GPCR) sense extracellular signals and activate different Guanine nucleotide binding proteins (G proteins). Upon activation, GPCRs can replace the GDP with GTP in the alpha subunit of G proteins. GTP binding modifies the conformation of G alpha proteins and activates them. The Regulator of G protein Signalling (RGS) proteins are GTPase Accelerating Proteins (GAPs) that can inhibit the G alpha subunit activity via their GAP activity. There are at least 25 different types of RGS proteins known. Several of these RGS proteins (1, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 17, 18, 19, 20, 21) can bind and stabilize the transition state for GTP hydrolysis of Guanine nucleotide binding protein G(i) subunit alpha (GNAI). Subsequently, this leads to GTP hydrolysis and inactivation of GNAI and terminating downstream signalling (Neubig & Siderovski DP 2002, Kach et al. 2012). The primary function of GNAI is the inhibition of adenylate cyclase.
Literature References
PubMed ID Title Journal Year
12120503 Regulators of G-protein signalling as new central nervous system drug targets

Neubig, RR, Siderovski, DP

Nat Rev Drug Discov 2002
18434541 Structural diversity in the RGS domain and its interaction with heterotrimeric G protein alpha-subunits

Kimple, AJ, Dowler, EF, Ball, LJ, Hutsell, SQ, Willard, FS, Soundararajan, M, Gileadi, C, Doyle, DA, Turnbull, AP, Higman, VA, Siderovski, DP, Schoch, GA, Fedorov, OY, Sundström, M

Proc. Natl. Acad. Sci. U.S.A. 2008
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