G Protein Families and Subunits

Figure 23.12 depicts the subunit structure of G proteins and their interactions, as affected by GTP and GDP. Several different forms of each G protein are known. In most forms, the subunit is prenylated (covalently bound to a 20 carbon isoprenoid moiety at the C-terminal cysteine). The subunit is covalently linked to myristic acid and is the subunit that contains both the guanine nucleotide-binding site and the GTPase activity.

Binding of GTP by the subunit causes it to dissociate from the other subunits and bind to adenylate cyclase. When GTP is hydrolyzed in the subunit, however, it dissociates from adenylate cyclase and reassociates with the other subunits.

Cholera and pertussis toxins catalyze the covalent addition of ADP-ribose to specific sites in the subunits of G s and G i, respectively. This modification inhibits GTPase action in the subunits and converts them to irreversible activators of adenylate cyclase. As a result, cAMP accumulates. In the intestine, the response to this is an uncontrollable secretion of water and sodium--causing severe diarrhea and dehydration.

At least four different subunits, five subunits, and 6 subunits are known, allowing for a large number of G proteins to be made from these combinations. Table 23.4 summarizes some of the properties of different G proteins.

The subunits of G proteins are part of a family of small GTP-binding proteins that are active when GTP is bound and inactive in the presence of GDP. This includes the Ras oncogene proteins (see here) and the GTP-binding elongation factors in protein synthesis (see here).

See also: G Proteins and Signal Transduction, G proteins in vision, Signal Transduction Agonists and Antagonists

INTERNET LINKS:

> 1. G Protein Receptor Coupled Database

> 2. G Protein Coupled Receptors Point Mutation Database