Activering en inactivatie van G-eiwitten

Heterotrimeric G-proteins are membrane-anchored proteins that cycle between GDP and GTP bound states and relay signals downstream of GPCRs.

Each G-protein comprises an alpha subunit, and beta and gamma subunits that are always bound together.

The alpha subunit is GDP bound and attached to the beta-gamma subunit in the resting state.

Upon ligand binding, the activated GPCR undergoes a conformational change, binds G-alpha, and exposes its nucleotide-binding site to trigger GDP/ GTP exchange.

Then G-alpha dissociates from the receptor and the beta-gamma subunits, to move across the membrane. Both G beta-gamma and GTP-bound G-alpha subunits can now individually bind and activate effectors like adenylyl cyclase and phospholipase C-beta.

The activated effectors release second messengers like cyclic adenosine monophosphate and inositol trisphosphate.

Once the GTP is hydrolyzed to GDP, G-alpha can no longer bind its effectors, and reassociates with the beta gamma subunits returning to the resting state.