GTPase - Heterotrimeric G Proteins

Heterotrimeric G Proteins

These G proteins are made from three subunits, with the G domain located on the largest one (the α unit); together with the two smaller subunits (β and γ units), they form a tightly associated protein complex. α and γ unit are associated with the membrane by lipid anchors. Heterotrimeric G proteins act as the specific reaction partners of G protein-coupled receptors. The GTPase is normally inactive. Upon receptor activation, the intracellular receptor domain activates the GTPase, which in turn activates other molecules of the signal transduction chain, either via the α unit or the βγ complex. Among the target molecules of the active GTPase are adenylate cyclase and ion channels. The heterotrimeric G proteins can be classified by sequence homology of the α unit into four families:

1. G_s family. These G proteins are used in the signal transduction of taste and smell. They always use the activation of adenylate cyclase as the next step in the signal chain. The _s stands for stimulation. Their function is permanently activated by the cholera toxin, which is the cause of the fatal effects of infection with Vibrio cholerae.
2. G_i family. The i stands for inhibition of the adenylate cyclase; another effector molecule for this protein family is phospholipase C. Also, G_t and G_g proteins are summarized under this label due to sequence homologies. G_t proteins, aka transducin, is used in the light recognition pathway in retina cells. G_g protein occurs in the taste recognition for bitter. Most G_i protein family members can be inhibited by the pertussis toxin of Bordetella pertussis.
3. G_q family. These proteins usually have phospholipase C as effector protein.
4. G₁₂ family. These G proteins can be activated by thromboxan receptors and thrombin receptors. Their effector proteins are unknown.

By combination of different α, β and γ subunits, a great variety (>1000) G proteins can be produced. GDP is not needed for GTP.