G Proteins

The full name of "G protein" is GTP-binding protein because in the active state it binds to GTP (guanosine triphosphate).  There are two types of G proteins: heterotrimeric G proteins and monomeric G proteins (or small G proteins). G-protein-coupled receptors are coupled to heterotrimeric G proteins. 

Figure 6-D-2.  The structure of heterotrimeric G protein, consisting of three subunits: a, b and g.  Note that in the inactive state, the a subunit binds to GDP (guanosine diphosphate).

The heterotrimeric G protein consists of three subunits: a, b and g.  Based on the differences in their genes, 20 a, 6 b and 12 g subunits have been identified.  Their molecular weights are in the following ranges:

• a subunit: 39 - 46 kD
• b subunit: 35 - 39 kD
• g subunit:  ~ 8 kD

In the inactive state, the a subunit binds to GDP and the three subunits are attached together (see above figure).  When the a subunit binds to GTP, its affinity to the bg subunits is decreased, resulting in their dissociation.  The separated a and/or bg subunits can then interact with their effectors.

Cycling of G protein between active and inactive states

Figure 6-D-3.  Cycling of G protein between active and inactive states.
(a) In the inactive state, G_a binds to GDP (guanosine diphosphate).
(b) Interaction between G_a and the agonist-stimulated receptor causes the release of GDP.  GTP then binds to the empty site because its concentration in the cell is higher than GDP.
(c) The GTP-bound G_a has low affinity to bg subunits, resulting in their dissociation.
(d) GTP is hydrolyzed to GDP because G_a has GTPase activity. 

The rate of GTP hydrolysis by G_a is regulated by a special class of proteins.  For more information, see 

Mammalian RGS (Regulators of G protein Signaling) Proteins - J. Biol. Chem., 1998.

The major unsolved question is how the agonist-receptor interaction activates G proteins.  Some models are discussed in 

G Protein-Coupled Receptors II.  Mechanism of Agonist Activation - J. Biol. Chem., 1998.