Final Answer:
The G-protein activation proceeds with the replacement of GDP by GTP as an intermediate step. This is a critical event in the activation cascade, initiating conformational changes in the G-protein and facilitating its interaction with downstream effectors.
Step-by-step explanation:
The activation of G-proteins involves a series of steps, and the replacement of GDP by GTP is a pivotal intermediate step. In this process, the inactive G-protein bound to GDP is activated when an external signal, such as ligand binding to a G-protein-coupled receptor (GPCR), induces the exchange of GDP for GTP. This exchange is catalyzed by guanine nucleotide exchange factors (GEFs). The GEF promotes the dissociation of GDP from the G-protein, creating a binding site for GTP. The high cellular concentration of GTP facilitates the binding of GTP to the G-protein, resulting in the formation of the active Gα-GTP complex.
The significance of this step lies in the conformational changes induced in the G-protein upon binding GTP. The transition to the Gα-GTP state triggers the dissociation of the Gα subunit from the Gβγ subunit, allowing both subunits to interact with downstream effectors and initiate intracellular signaling cascades. This activation mechanism ensures a rapid and precise cellular response to external signals. The hydrolysis of GTP to GDP by the intrinsic GTPase activity of the Gα subunit eventually terminates the signaling event and restores the G-protein to its inactive state, ready for the next activation cycle. The replacement of GDP by GTP, therefore, serves as a molecular switch in G-protein signaling pathways.