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.^[1]

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Alpha subunits

G_α subunits consist of two domains, the GTPase domain, and the alpha-helical domain. There exist at least 20 different G_α subunits, which are separated into several main families:

• G_αs or simply G_s (stimulatory) - activates adenylate cyclase to increase cAMP synthesis
  • GNAS
• G_αi or simply G_i (inhibitory) - inhibits adenylate cyclase
  • GNAI1, GNAI2, GNAI3, GNAZ, GNAO1
• G_olf (olfactory) - couples to olfactory receptors
  • GNAL
• G_t (transducin) - transduces visual signals in conjunction with rhodopsin in the retina
  • GNAT1, GNAT2, GNAT3
• G_q - stimulates phospholipase C
  • GNAQ, GNA11, GNA14, GNA15
• The G_12/13 family - important for regulating (via guanine nucleotide exchange factors) the cytoskeleton, cell junctions, and other processes related to movements
  • GNA12, GNA13

Beta-gamma complex

The β and γ subunits are closely bound to one another and are referred to as the beta-gamma complex. The G_βγ complex is released from the G_α subunit after its GDP-GTP exchange.

Function

The free G_βγ complex can act as a signaling molecule itself, by activating other second messengers or by gating ion channels directly.

For example, the G_βγ complex, when bound to histamine receptors, can activate phospholipase A₂. G_βγ 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.

Genes

• G_β genes: GNB1, GNB2, GNB3, GNB4, GNB5, GNB1L, GNB2L1

• G_γ genes: GNGT1, GNGT2, GNG2, GNG3, GNG4, GNG5, GNG7, GNG8, GNG10, GNG11, GNG12, GNG13

References