G-protein activation.2Fdeactivation cycle G protein–coupled receptor

cartoon depicting heterotrimeric g-protein activation/deactivation cycle in context of gpcr signaling

when receptor inactive, gef domain may bound inactive α-subunit of heterotrimeric g-protein. these g-proteins trimer of α, β, , γ subunits (known gα, gβ, , gγ, respectively) rendered inactive when reversibly bound guanosine diphosphate (gdp) (or, alternatively, no guanine nucleotide) active when bound guanosine triphosphate (gtp). upon receptor activation, gef domain, in turn, allosterically activates g-protein facilitating exchange of molecule of gdp gtp @ g-protein s α-subunit. cell maintains 10:1 ratio of cytosolic gtp:gdp exchange gtp ensured. @ point, subunits of g-protein dissociate receptor, each other, yield gα-gtp monomer , tightly interacting gβγ dimer, free modulate activity of other intracellular proteins. extent may diffuse, however, limited due palmitoylation of gα , presence of isoprenoid moiety has been covalently added c-termini of gγ.

because gα has slow gtp→gdp hydrolysis capability, inactive form of α-subunit (gα-gdp) regenerated, allowing reassociation gβγ dimer form resting g-protein, can again bind gpcr , await activation. rate of gtp hydrolysis accelerated due actions of family of allosteric modulating proteins called regulators of g-protein signaling, or rgs proteins, type of gtpase-activating protein, or gap. in fact, many of primary effector proteins (e.g., adenylate cyclases) become activated/inactivated upon interaction gα-gtp have gap activity. thus, @ stage in process, gpcr-initiated signaling has capacity self-termination.