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Monod-Wyman-Changeux Analysis of Ligand-Gated Ion Channel Mutants.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Einav, Tal Phillips, Rob |
| Copyright Year | 2017 |
| Abstract | 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. |
| Starting Page | 3813 |
| Ending Page | 3824 |
| Page Count | 12 |
| File Format | PDF HTM / HTML |
| arXiv | 1701.06122 |
| Alternate Webpage(s) | http://www.rpgroup.caltech.edu/publications/Einav2017.pdf |
| Alternate Webpage(s) | https://arxiv.org/pdf/1701.06122v1.pdf |
| Alternate Webpage(s) | http://authors.library.caltech.edu/73863/3/jp6b12672_si_001.pdf |
| Alternate Webpage(s) | http://authors.library.caltech.edu/73863/5/nihms857725.pdf |
| Alternate Webpage(s) | http://www.rpgroup.caltech.edu/publications/Einav2017_SI_1.pdf |
| PubMed reference number | 28134524v1 |
| Alternate Webpage(s) | https://doi.org/10.1021/acs.jpcb.6b12672 |
| DOI | 10.1021/acs.jpcb.6b12672 |
| Journal | The journal of physical chemistry. B |
| Volume Number | 121 |
| Issue Number | 15 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Acetylcholine Cholinergic Receptors Class Computation (action) Dynamic Range Gated Blood-Pool Imaging Gated Ion Channel Iontophoresis Ligand Binding Ligands Mutation Nicotinic Receptors Phenotype Subgroup mutant |
| Content Type | Text |
| Resource Type | Article |
