Ion permeation in K + channels occurs by direct Coulomb knock-on

Author:

Köpfer David A.1,Song Chen2,Gruene Tim3,Sheldrick George M.3,Zachariae Ulrich45,de Groot Bert L.1

Affiliation:

1. Biomolecular Dynamics Group, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany.

2. Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.

3. Department of Structural Chemistry, University of Göttingen, 37077 Göttingen, Germany.

4. School of Engineering, Physics and Mathematics, University of Dundee, Dundee DD1 4HN, UK.

5. College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.

Abstract

Potassium channels selectively conduct K + ions across cellular membranes with extraordinary efficiency. Their selectivity filter exhibits four binding sites with approximately equal electron density in crystal structures with high K + concentrations, previously thought to reflect a superposition of alternating ion- and water-occupied states. Consequently, cotranslocation of ions with water has become a widely accepted ion conduction mechanism for potassium channels. By analyzing more than 1300 permeation events from molecular dynamics simulations at physiological voltages, we observed instead that permeation occurs via ion-ion contacts between neighboring K + ions. Coulomb repulsion between adjacent ions is found to be the key to high-efficiency K + conduction. Crystallographic data are consistent with directly neighboring K + ions in the selectivity filter, and our model offers an intuitive explanation for the high throughput rates of K + channels.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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