Guanine nucleotide binding proteins (
G proteins) are membrane-associated,
heterotrimeric proteins composed of three subunits: alpha, beta, and gamma. G
proteins and their
receptors (
GPCRs) form one of the most prevalent
signalling systems in
mammalian cells, regulating systems as diverse as sensory perception,
cell growth and hormonal
regulation. At the
cell surface, the binding of
ligands such as
hormones and
neurotransmitters to a GPCR activates the
receptor by causing a
conformational change, which in
turn activates the bound G protein on the intracellular-side of the
membrane. The activated
receptor promotes the exchange of bound GDP for GTP on the G protein alpha subunit. GTP binding changes the
conformation of switch regions within the alpha subunit, which allows the bound trimeric G protein (inactive) to be released from the receptor, and to dissociate into active alpha subunit (GTP-bound) and beta/gamma
dimer. The alpha subunit and the beta/gamma dimer go on to activate distinct downstream effectors, such as adenylyl cyclase, phosphodiesterases,
phospholipase C, and
ion channels. These
effectors in turn
regulate the
intracellular concentrations of secondary messengers, such as cAMP, diacylglycerol,
sodium or
calcium cations, which ultimately lead to a
physiological response, usually via the downstream regulation of
gene transcription. The cycle is completed by the
hydrolysis of alpha subunit-bound GTP to GDP, resulting in the re-association of the alpha and beta/gamma
subunits and their binding to the receptor, which terminates the signal. The length of the G protein signal is controlled by the duration of the GTP-bound alpha subunit, which can be regulated by RGS (regulator of G protein signalling) proteins or by
covalent modifications.