Tipping Cell Signaling Pathways by Salts.

Mechanistic Insights into Allosteric Regulation of the A2A Adenosine G protein-Coupled Receptor by Physiological Cations

Libin Ye1,2, Chris Neale3, Adnan Sljoka4, Brent Lyda5, Dmitry Pichugin1,2, Nobuyuki Tsuchimura4, Sacha T. Larda1,2, Régis Pomès2,6, Angel E. García3, Oliver P. Ernst2,7, Roger K. Sunahara5, R. Scott Prosser1,2,*

In a recent paper appearing in Nature Communications, Libin Ye (Prosser lab) and co-authors reveal the delicate balance between inactive states and activation intermediates by allosteric factors such as sodium (a so-called negative allosteric modulator) and magnesium ions (positive allosteric modulators). The role of sodium in the regulation of GPCRs is currently a hot topic as more and more receptors are found to possess a conserved sodium binding site. Nature takes advantage of the abundance of sodium in cells and it’s inherent concentration gradient to help regulate the majority of class A GPCRs.