What initiates the G-protein cycle?

• A. Conformational change of the receptor
• B. The alpha subunit dissociates from beta-gamma
• C. The heterotrimer reassembles
• D. GTP replaces GDP on the alpha subunit

Answer: (D)

The G-protein cycle begins when the GDP bound to the alpha subunit is exchanged for GTP, a step driven by the activated receptor acting as a guanine nucleotide exchange factor. This nucleotide swap is the trigger that puts the G protein into motion: once GTP is bound, the alpha subunit changes shape and dissociates from the beta-gamma complex, allowing both parts to interact with different downstream effectors. After signaling, the intrinsic GTPase activity of the alpha subunit hydrolyzes GTP back to GDP, enabling the subunits to reassociate into the inactive heterotrimer and reset the cycle. The receptor’s conformational change is necessary to start the process, but the actual initiation of signaling is the GDP-to-GTP exchange on the alpha subunit.