Editing G protein-coupled receptor (section)

=== Conformational change ===

[[File:Beta2Receptor-with-Gs.png|right|thumb|300px|Crystal structure of activated beta-2 adrenergic receptor in complex with G<sub>s</sub>([[w:Protein Data Bank|PDB]] entry [https://web.archive.org/web/20180128134132/https://www.rcsb.org/structure/3SN6 3SN6]). The receptor is colored red, Gα green, Gβ cyan, and Gγ yellow. The C-terminus of Gα is located in a cavity created by an outward movement of the cytoplasmic parts of TM5 and 6.]]

The [[signal transduction|transduction of the signal]] through the membrane by the receptor is not completely understood. It is known that in the inactive state, the GPCR is bound to a [[heterotrimeric G protein]] complex. Binding of an agonist to the GPCR results in a [[conformational change]] in the receptor that is transmitted to the bound G<sub>α</sub> subunit of the heterotrimeric G protein via [[protein dynamics#Global flexibility: multiple domains|protein domain dynamics]]. The activated G<sub>α</sub> subunit exchanges [[guanosine triphosphate|GTP]] in place of [[guanosine diphosphate|GDP]] which in turn triggers the dissociation of G<sub>α</sub> subunit from the G<sub>βγ</sub> dimer and from the receptor. The dissociated G<sub>α</sub> and G<sub>βγ</sub> subunits interact with other intracellular proteins to continue the signal transduction cascade while the freed GPCR is able to rebind to another heterotrimeric G protein to form a new complex that is ready to initiate another round of signal transduction.<ref name="pmid17095603">{{cite journal | vauthors = Digby GJ, Lober RM, Sethi PR, Lambert NA | title = Some G protein heterotrimers physically dissociate in living cells | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 103 | issue = 47 | pages = 17789–94 | date = November 2006 | pmid = 17095603 | pmc = 1693825 | doi = 10.1073/pnas.0607116103 | bibcode = 2006PNAS..10317789D | doi-access = free }}</ref>

It is believed that a receptor molecule exists in a conformational [[dynamic equilibrium|equilibrium]] between active and inactive biophysical states.<ref>{{cite journal |vauthors=Rubenstein LA, Lanzara RG |title=Activation of G protein-coupled receptors entails cysteine modulation of agonist binding |journal= Journal of Molecular Structure: Theochem|year=1998 |volume=430 |pages=57–71 |url=https://cogprints.org/4095/ |doi=10.1016/S0166-1280(98)90217-2 |access-date=14 January 2006 |archive-date=16 May 2011 |archive-url=https://web.archive.org/web/20110516061030/https://cogprints.org/4095/ |url-status=live }}</ref> The binding of ligands to the receptor may shift the equilibrium toward the active receptor states. Three types of ligands exist: Agonists are ligands that shift the equilibrium in favour of active states; [[inverse agonist]]s are ligands that shift the equilibrium in favour of inactive states; and neutral antagonists are ligands that do not affect the equilibrium. It is not yet known how exactly the active and inactive states differ from each other.{{cn|date=April 2025}}