Question

GTPY S is a form of GTP that cannot be hydrolyzed to GDP. How would GPCR signaling through the B 2- adrenergic receptor (epinephrine receptor) be affected in the presence of GTPY S (instead of regular GTP)? CAMP levels would decrease as GTPYS locks the G-protein is in the inactive state. CAMP levels would decrease because GTPYS interferes with epinephrine binding to the receptor. CAMP levels would be similar as with GTP. The phosphorylation state of this nucleotide does not influence G-protein activity. CAMP levels would increase due to constant activation of adenylate cyclase by the G-protein

Answer 1

Epinephrine receptors are G-protein coupled receptors which is the largest gene family in the human genome. All of them signal through coupling to Gαs G-proteins, adenylyl cyclase , and cAMP-dependent protein kinase A. Binding of the receptor to its ligand induce  a rise in the intracellular level of cAMP, resulting from activation of adenylyl cyclase.

In absence of ligand, the α subunit of G_s protein (G_sα) is bound to GDP. Ligand binding changes its conformation, causing it to bind to the trimeric G_s protein in such a way that GDP is displaced from G_sα and GTP is bound. The G_sα·GTP complex, which dissociates from the G_bγ complex, then binds to and activates adenylyl cyclase. The GTP bound to G_sα is subsequently hydrolyzed to GDP leading to the inactivation of adenylyl cyclase. Thus, in the absence of GTP hydrolysis due to binding of GTP gamma S, cAMP would increase due to constant activation of adenylate cyclase by G-proteins.