A Novel Voltage Sensor in the Orthosteric Binding Site of the M2 Muscarinic Receptor

作者：Barchad Avitzur Ofra; Priest Michael F; Dekel Noa; Bezanilla Francisco; Parnas Hanna; Ben Chaim Yair^*

来源：Biophysical Journal, 2016, 111(7): 1396-1408.

DOI：10.1016/j.bpj.2016.08.035

G protein-coupled receptors (GPCRs) mediate many signal transduction processes in the body. The discovery that these receptors are voltage-sensitive has changed our understanding of their behavior. The M2 muscarinic acetylcholine receptor (M2R) was found to exhibit depolarization-induced charge movement-associated currents, implying that this prototypical GPCR possesses a voltage sensor. However, the typical domain that serves as a voltage sensor in voltage-gated channels is not present in GPCRs, making the search for the voltage sensor in the latter challenging. Here, we examine the M2R and describe a voltage sensor that is comprised of tyrosine residues. This voltage sensor is crucial for the voltage dependence of agonist binding to the receptor. The tyrosine-based voltage sensor discovered here constitutes a noncanonical by which membrane proteins may sense voltage.

• 出版日期2016-10-4