G protein

Think of a G protein as a molecular switch wired between a doorbell and the lights inside a house. Pressing the doorbell (a receptor catching its signal) flips the switch on; the switch then turns on the lights (the effector enzyme or channel) for a while before automatically clicking off. The on/off timing is built into the switch itself.

Mechanistically, the classic heterotrimeric G protein has three subunits — alpha, beta, and gamma. At rest the alpha subunit holds GDP. When a G-protein-coupled receptor is activated by its ligand, it pries open the alpha subunit so it swaps GDP for GTP; the GTP-bound alpha then separates from the beta-gamma pair, and both parts go on to regulate effectors. The alpha subunit slowly hydrolyzes GTP back to GDP, which shuts itself off and lets the trimer reassemble.

Families of alpha subunits define what the G protein does: Gs stimulates adenylyl cyclase, Gi inhibits it, and Gq activates phospholipase C. This is why a single drug class can produce opposite effects in different tissues — it depends on which G protein the receptor couples to. Many important medicines (beta-blockers, opioids, antihistamines, many antipsychotics) ultimately work by changing the activity of G-protein-coupled receptors.

A caveat: the heterotrimeric G proteins described here are distinct from the small monomeric G proteins (such as Ras) that govern growth and cytoskeletal signaling. Both bind GTP and act as switches, but they sit in different pathways.