Signal transduction

How does GTP function in a G-protein coupled receptor?

Answer: GTP is a source of chemical energy that determines if the G-protein is active or inactive.

GTP in G-protein couple receptor

Guanosine triphosphate (GTP) is an important step in the process of intracellular signaling of a G-protein coupled receptor (GPCR). GPCRs, or seven transmembrane (7TM) receptors, are expressed on the cell surface. When a ligand binds to the receptor, an intracellular cascade is triggered through a G-protein that can be activated when a GTP molecule is bound, and inactivated when a GDP molecule is bound.

There are two different types of G proteins. The large G-proteins consist of three main parts, an alpha, beta, and gamma subunit. Generally, the alpha subunit is thought of being the major actor in intracellular signaling pathways. After the ligand binds to the receptor, a GTP molecule will attach to the G-protein, then the G alpha subunit will dissociate from the G beta gamma subunit, which are tightly associated.

The G alpha subunit can have a variety of functions. The G alpha i subunit is the inhibitory signaling protein, and inhibits the cell by decreasing the activity of cyclic AMP (cAMP). G alpha s is the opposite, and stimulates the cell by increasing cAMP activity. G alpha q can be excitatory or inhibitory, depending on the downstream signaling of the particular cell. It activates phospholipase C, which modulates ion channels in different ways.

In addition to playing an important role as a second messenger, GTP is also a necessary source of energy in the process of translation as well as creation of glucose.