Heterotrimeric G protein
"G protein" usually refers to the membrane-associated heterotrimeric G proteins, sometimes referred to as the "large" G proteins. These proteins are activated by G protein-coupled receptors and are made up of alpha (α), beta (β) and gamma (γ) subunits.
Gα subunits consist of two domains, the GTPase domain, and the alpha-helical domain. There exist at least 20 different Gα subunits, which are separated into several main families:
- Gαs or simply Gs (stimulatory) - activates adenylate cyclase to increase cAMP synthesis
- Gαi or simply Gi (inhibitory) - inhibits adenylate cyclase
- Golf (olfactory) - couples to olfactory receptors
- Gt (transducin) - transduces visual signals in conjunction with rhodopsin in the retina
- Gq - stimulates phospholipase C
- The G12/13 family - important for regulating (via guanine nucleotide exchange factors) the cytoskeleton, cell junctions, and other processes related to movements
The β and γ subunits are closely bound to one another and are referred to as the beta-gamma complex. The Gβγ complex is released from the Gα subunit after its GDP-GTP exchange.
The free Gβγ complex can act as a signaling molecule itself, by activating other second messengers or by gating ion channels directly.
For example, the Gβγ complex, when bound to histamine receptors, can activate phospholipase A2. Gβγ complexes bound to muscarinic acetylcholine receptors, on the other hand, directly open G-protein coupled inward rectifying potassium channels (GIRKs). They can also activate L-type calcium channels, as in H3 receptor pharmacology.