In GPCR signaling, which step occurs immediately after a ligand binds to the receptor?

• A. The alpha subunit dissociates from the beta-gamma subunit to activate the effector
• B. GTP replaces GDP on the alpha subunit
• C. Conformational change/activation of the receptor occurs
• D. The heterotrimer reassembles and recouples to the receptor

Answer: (C)

When a ligand binds a GPCR, the receptor shifts from an inactive to an active conformation. This conformational change is what allows the receptor to engage the heterotrimeric G protein and act as a guanine nucleotide exchange factor, promoting the exchange of GDP for GTP on the Gα subunit. Once GTP binds, the Gα–GTP dissociates from the Gβγ dimer and both components go on to regulate downstream effectors. So the very first event after ligand binding is the receptor’s conformational activation; the GDP-to-GTP exchange, subunit dissociation, and downstream signaling occur in the subsequent steps.