Mechanism of pore opening in the calcium-activated chloride channel TMEM16A
| Autor: | Andy K.M. Lam, Raimund Dutzler |
|---|---|
| Přispěvatelé: | University of Zurich, Lam, Andy K M, Dutzler, Raimund |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Models
Molecular Protein Conformation alpha-Helical 0301 basic medicine Patch-Clamp Techniques genetic structures General Physics and Astronomy Gating 0302 clinical medicine Protein structure Poisson Distribution Chloride channels Multidisciplinary Chemistry 3100 General Physics and Astronomy Neoplasm Proteins Chloride channel Permeation and transport Ion Channel Gating Monte Carlo Method Protein Binding Cations Divalent Science Allosteric regulation Kinetics 610 Medicine & health 1600 General Chemistry Article General Biochemistry Genetics and Molecular Biology Ion 03 medical and health sciences Allosteric Regulation Chlorides 1300 General Biochemistry Genetics and Molecular Biology 10019 Department of Biochemistry Humans Patch clamp Binding site Anoctamin-1 Ion transport Binding Sites General Chemistry HEK293 Cells 030104 developmental biology Mutation Biophysics 570 Life sciences biology Calcium 030217 neurology & neurosurgery |
| Zdroj: | Nature Communications, Vol 12, Iss 1, Pp 1-14 (2021) Nature Communications |
| DOI: | 10.5167/uzh-209840 |
| Popis: | The anion channel TMEM16A is activated by intracellular Ca2+ in a highly cooperative process. By combining electrophysiology and autocorrelation analysis, we investigated the mechanism of channel activation and the concurrent rearrangement of the gate in the narrow part of the pore. Features in the fluctuation characteristics of steady-state current indicate the sampling of intermediate conformations that are successively occupied during gating. The initial step is related to conformational changes induced by Ca2+ binding, which is ensued by rearrangements that open the pore. Mutations in the gate shift the equilibrium of transitions in a manner consistent with a progressive destabilization of this region during pore opening. We come up with a mechanism of channel activation where the binding of Ca2+ induces conformational changes in the protein that, in a sequential manner, propagate from the binding site and couple to the gate in the narrow pore to allow ion permeation. The anion channel TMEM16A is activated by intracellular Ca2+ in a highly cooperative process. Here authors combine electrophysiology and autocorrelation analysis to observe the sampling of intermediate conformations during gating. |
| Databáze: | OpenAIRE |
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