Translocation Mechanism of Allosteric Sodium Ions in β 2 -Adrenoceptor.

The allosteric modulation of G-protein-coupled receptors (GPCRs) by sodium ions has received significant attention as the crystal structures of several receptors show the binding of sodium ions (Na + ) at the conserved D 2.50 . Theoretical studies have shown that extracellular Na + would enter the allosteric D 2.50 via the orthosteric site. However, it remains unclear how the bound allosteric Na + would leave the GPCRs. In this study, we performed molecular dynamics (MD) simulations to illustrate the energy barriers of Na + transfer through the transmembrane helix bundle of β 2 AR. In contrast to the postulations from other GPCRs, the translocation of this allosteric Na + into the intracellular side is found to be significantly difficult. Hence, the translocation direction could be receptor-specific.