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Biophys J. 2016 Oct 4;111(7):1396-1408. doi: 10.1016/j.bpj.2016.08.035.

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

Author information

1
Department of Neurobiology, Institute of Life Sciences, The Hebrew University, Jerusalem, Israel.
2
Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, Illinois.
3
Natural and Life Sciences, Open University of Israel, Raanana, Israel. Electronic address: yairbc@openu.ac.il.

Abstract

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.

PMID:
27705763
PMCID:
PMC5052511
DOI:
10.1016/j.bpj.2016.08.035
[Indexed for MEDLINE]
Free PMC Article

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