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.
| Original language | English |
|---|---|
| Pages (from-to) | 1396-1408 |
| Number of pages | 13 |
| Journal | Biophysical Journal |
| Volume | 111 |
| Issue number | 7 |
| DOIs | |
| State | Published - 4 Oct 2016 |
Bibliographical note
Funding Information:This work was supported by a grant from the National Institute for Psychobiology in Israel, founded by the Charles E. Smith Family, to Y.B.-C., by an internal research grant from the Open University in Israel to Y.B.-C., and by National Institutes of Health grant R01-GM030376 to F.B., with extra support to M.F.P. from F31-NS081954. O.B.-A. was supported by a fellowship from the Open University in Israel.
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© 2016 Biophysical Society