Structural Mechanisms of Voltage Sensing in G Protein-Coupled Receptors

• DOI: 10.1016/j.str.2016.04.007
• Publication Date: 2016-05-21T08:24:48Z
• Authors: Owen N. Vickery; Jan-Philipp Machtens; Giulia Tamburrino; Daniel Seeliger; Ulrich Zachariae
• Keywords: Structural Biology

G-protein-coupled receptors (GPCRs) form the largest superfamily of membrane proteins and one-third all drug targets in humans. A number recent studies have reported evidence for substantial voltage regulation GPCRs. However, structural basis GPCR sensing has remained enigmatic. Here, we present atomistic simulations on δ-opioid M2 muscarinic receptors, which suggest a mechanistic explanation observed voltage-induced functional effects. The reveal that position an internal Na(+) ion, recently detected to bind highly conserved aqueous pocket receptor crystal structures, strongly responds changes. movements give rise gating charges excellent agreement with previous experimental recordings. Furthermore, free energy calculations show these rearrangements can be induced by physiological voltages. Due its role function signal bias, repositioning important general implications transduction