Structural Mechanisms of Voltage Sensing in G Protein-Coupled Receptors.

ABSTRACT: G-protein-coupled receptors (GPCRs) form the largest superfamily of membrane proteins and one-third of all drug targets in humans. A number of recent studies have reported evidence for substantial voltage regulation of GPCRs. However, the structural basis of GPCR voltage sensing has remained enigmatic. Here, we present atomistic simulations on the δ-opioid and M2 muscarinic receptors, which suggest a structural and mechanistic explanation for the observed voltage-induced functional effects. The simulations reveal that the position of an internal Na(+) ion, recently detected to bind to a highly conserved aqueous pocket in receptor crystal structures, strongly responds to voltage changes. The movements give rise to gating charges in excellent agreement with previous experimental recordings.

SUBMITTER: Vickery ON 

PROVIDER: S-EPMC4906246 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature