Editing G protein-coupled receptor (section)

===G-protein activation/deactivation cycle===
[[File:GPCR cycle.jpg|thumb|500px|Cartoon depicting the heterotrimeric G-protein activation/deactivation cycle in the context of GPCR signaling]]
{{See also|G protein}}
When the receptor is inactive, the [[guanine nucleotide exchange factor|GEF]] domain may be bound to an also inactive α-subunit of a [[heterotrimeric G-protein]]. These "G-proteins" are a [[protein trimer|trimer]] of α, β, and γ subunits (known as Gα, Gβ, and Gγ, respectively) that is rendered inactive when reversibly bound to [[Guanosine diphosphate]] (GDP) (or, alternatively, no guanine nucleotide) but active when bound to [[guanosine triphosphate]] (GTP). Upon receptor activation, the GEF domain, in turn, [[allosterically]] activates the G-protein by facilitating the exchange of a molecule of GDP for GTP at the G-protein's α-subunit. The cell maintains a 10:1 ratio of cytosolic GTP:GDP so exchange for GTP is ensured. At this point, the subunits of the G-protein dissociate from the receptor, as well as each other, to yield a Gα-GTP [[monomer]] and a tightly interacting [[G beta-gamma complex|Gβγ dimer]], which are now free to modulate the activity of other intracellular proteins. The extent to which they may [[diffuse]], however, is limited due to the [[palmitoylation]] of Gα and the presence of an [[isoprenoid]] moiety that has been [[covalent bond|covalently]] added to the C-termini of Gγ.{{cn|date=April 2025}}

Because Gα also has slow [[GTP-ase|GTP→GDP hydrolysis]] capability, the inactive form of the α-subunit (Gα-GDP) is eventually regenerated, thus allowing reassociation with a Gβγ dimer to form the "resting" G-protein, which can again bind to a GPCR and await activation. The rate of GTP hydrolysis is often accelerated due to the actions of another family of allosteric modulating proteins called [[regulator of G protein signaling|regulators of G-protein signaling]], or RGS proteins, which are a type of [[GTPase-activating protein]], or GAP. In fact, many of the primary [[Effector (biology)|effector]] proteins (e.g., [[adenylate cyclase]]s) that become activated/inactivated upon interaction with Gα-GTP also have GAP activity. Thus, even at this early stage in the process, GPCR-initiated signaling has the capacity for self-termination.{{cn|date=April 2025}}