<p>Guanine nucleotide binding proteins (G proteins) are membrane-associated, heterotrimeric proteins composed of three subunits: alpha (<db_xref db="INTERPRO" dbkey="IPR001019"/>), beta (<db_xref db="INTERPRO" dbkey="IPR001632"/>) and gamma (<db_xref db="INTERPRO" dbkey="IPR001770"/>) [<cite idref="PUB00015169"/>]. 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 [<cite idref="PUB00015166"/>]. 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 [<cite idref="PUB00015168"/>]. 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 (<db_xref db="INTERPRO" dbkey="IPR000342"/>) or by covalent modifications [<cite idref="PUB00015170"/>].</p><p>There are several isoforms of each subunit, many of which have splice variants, which together can make up hundreds of combinations of G proteins. The specific combination of subunits in heterotrimeric G proteins affects not only which receptor it can bind to, but also which downstream target is affected, providing the means to target specific physiological processes in response to specific external stimuli [<cite idref="PUB00015171"/>, <cite idref="PUB00015172"/>]. G proteins carry lipid modifications on one or more of their subunits to target them to the plasma membrane and to contribute to protein interactions.</p><p>This family consists of the I class (inhibitory) G protein alpha subunit, which includes G(I)alpha, G(O)alpha, G(T)alpha and G(Z)alpha. G(I)alpha proteins were originally identified by their receptor-mediated inhibition of the cAMP-generating enzyme adenylyl cyclase. G(O)alpha proteins are extremely abundant and are predominantly expressed in the brain, where they are known to couple receptors such as the M2 acetylcholine receptor to neuronal potassium and calcium channels, and have been implicated in membrane trafficking [<cite idref="PUB00015181"/>]. The G(T)alpha protein, transducin, is responsible for transducing the light response in vertebrate retinas, which is initiated by the activation of rhodopsin or cone opsin by light and is transduced through transducin, which activates cGMP-phosphodiesterase, causing the cGMP-gated sodium channel to close and generating a nerve impulse through hyperpolarisation of cell membranes [<cite idref="PUB00014096"/>]. G(Z)alpha proteins are involved in calcium mobilisation [<cite idref="PUB00015183"/>].</p> G-protein alpha subunit, group I