InterPro domain: IPR011025

Guanine nucleotide binding proteins (G proteins) are membrane-associated, heterotrimeric proteins composed of three subunits: alpha ( IPR001019 ), beta ( IPR001632 ) and gamma ( IPR001770 ) [ 1 ]. G proteins act as signal transducers, relaying a signal from a ligand-activated GPCR (G protein-coupled receptor) to an enzyme or ion channel effector. The activated GPCR promotes the exchange of GDP for GTP on the G protein alpha subunit, allowing the trimeric G protein to be released from the receptor and to dissociate into active (GTP-bound) alpha subunit and beta/gamma dimer, both of which activate distinct downstream effectors. There are several isoforms of each subunit, which together can makeup hundreds of combinations of G proteins, each one linking a specific receptor to a certain effector.

The heterotrimeric G protein alpha subunit is composed of two domains: a GTP-binding domain and a helical insertion domain. The GTP-binding domain is homologous to Ras-like small GTPases, and includes switch regions I and II, which change conformation during activation. The helical insertion domain is inserted into the GTP-binding domain before switch region I, and is unique to heterotrimeric G proteins. This helical insertion domain functions to sequester the guanine nucleotide at the interface with the GTP-binding domain and must be displaced to enable nucleotide dissociation [ 2 ]. This superfamily represents the G protein alpha subunit helical insertion domain.

1. Biochemistry of transmembrane signaling mediated by trimeric G proteins. Physiol Res 53 Suppl 1, S141-52
2. Activation of G-protein Galpha subunits by receptors through Galpha-Gbeta and Galpha-Ggamma interactions. Trends Biochem. Sci. 28, 13-7