RT Journal Article
SR Electronic
T1 Monod-Wyman-Changeux Analysis of Ligand-Gated Ion Channel Mutants
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 102194
DO 10.1101/102194
A1 Tal Einav
A1 Rob Phillips
YR 2017
UL http://biorxiv.org/content/early/2017/01/22/102194.abstract
AB We present a framework for computing the gating properties of ligand-gated ion channel mutants using the Monod-Wyman-Changeux (MWC) model of allostery. We derive simple analytic formulas for key functional properties such as the leakiness, dynamic range, half-maximal effective concentration ([EC50]), and effective Hill coefficient, and explore the full spectrum of phenotypes that are accessible through mutations. Specifically, we consider mutations in the channel pore of nicotinic acetylcholine receptor (nAChR) and the ligand binding domain of a cyclic nucleotide-gated (CNG) ion channel, demonstrating how each mutation can be characterized as only affecting a subset of the biophysical parameters. In addition, we show how the unifying perspective offered by the MWC model allows us, perhaps surprisingly, to collapse the plethora of dose-response data from different classes of ion channels into a universal family of curves.