G alpha (i)–i1/i2/i3 in G (i):RGS complex is inactivated

Stable Identifier
Reaction [transition]
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) are GTPase Accelerating Proteins (GAPs) that can directly inhibit the G alpha subunit 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 of Guanine nucleotide binding protein G(i) subunit alpha (GNAI). Following this, the RGS domain of the proteins exert GAP activity on GNAI and allosterically modulate residues within G-alpha subunit to accelerate the intrinsic GTPase activity that hydrolyses GTP to GDP. This inactivates GNAI and terminates downstream signalling (Neubig & Siderovski 2002, Kach et al. 2012).

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
Catalyst Activity

GTPase activity of G alpha (i):GTP:RGS [plasma membrane]

Orthologous Events
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