Allosteric sodium: a key co-factor in class A GPCR signaling.

Trends in biochemical sciences

PubMedID: 24767681

Katritch V, Fenalti G, Abola EE, Roth BL, Cherezov V, Stevens RC. Allosteric sodium: a key co-factor in class A GPCR signaling. Trends Biochem Sci. 2014;.
Despite their functional and structural diversity, G-protein-coupled receptors (GPCRs) share a common mechanism of signal transduction via conformational changes in the seven-transmembrane (7TM) helical domain. New major insights into this mechanism come from the recent crystallographic discoveries of a partially hydrated sodium ion that is specifically bound in the middle of the 7TM bundle of multiple class A GPCRs. This review discusses the remarkable structural conservation and distinct features of the Na(+) pocket in this most populous GPCR class, as well as the conformational collapse of the pocket on receptor activation. New insights help to explain allosteric effects of sodium on GPCR agonist binding and activation, and highlight its role as a key co-factor in class A GPCR function.