Question

A GDP analog that can't be converted to GTP was added to a cell. The GDP analog otherwise behaves the same as authentic GDP. When g-proteins bind to the GDP analog, they are inactive, just like when they bind authentic GDP.  This cell has authentic GDP and plenty of GTP as well. What impact would this GDP analog have on the phosphoinositide (IP₃) and growth factor pathways if it were bound to the g-proteins? Pick the best available answer.

		The g-proteins in both pathways would likely be readily activated when the appropriate receptors are bound by their respective ligands because the GDP analog behaves like authentic GDP (other than it cannot be used to make GTP).
		The g-proteins in both pathways would NOT be readily activated when the appropriate receptors are bound by their respective ligands since GTP can't be made from the analog.

Answer 1

The g-proteins in both pathways would NOT be readily activated when the appropriate receptors are bound by their respective ligands since GTP can't be made from the analog. This is the correct answer.

G-protein activity is regulated by the binding and hydrolysis of GTP by the alpha subunit. Only the GTP-bound alpha subunit is active. The binding of GTP changes the conformation of ‘switch’ regions within the alpha subunit, which allows the bound trimeric G protein (inactive) to be released from the receptor, and to dissociate into active ? subunit (GTP-bound) and ?? dimer.  The ? subunit and the ?? dimer go on to activate distinct downstream effectors, such as adenylyl cyclase, phosphodiesterases, phospholipase C, Src, and ion channels.  These effectors in turn regulate the intracellular concentrations of secondary messengers, such as cAMP, cGMP, diacylglycerol, IP3, DAG, arachidonic acid, sodium, potassium or calcium cations, which ultimately lead to a physiological response, usually via the downstream regulation of gene transcription. A GDP-bound ? subunit is inactive, because the ‘switch’ regions in the a subunit are free to make contacts with the bg dimer to form a stable complex that does not readily allow GDP dissociation.