title: Ion permeation in K⁺ channels occurs by direct Coulomb knock-on.
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.
authors.affiliation: Biomolecular Dynamics Group, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany.
authors.forename: David A
authors.initials: DA
authors.lastname: Köpfer
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK. sc3210@gmail.com u.zachariae@dundee.ac.uk bgroot@gwdg.de.
authors.forename: Chen
authors.initials: C
authors.lastname: Song
authors.affiliation: Department of Structural Chemistry, University of Göttingen, 37077 Göttingen, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Gruene
authors.affiliation: Department of Structural Chemistry, University of Göttingen, 37077 Göttingen, Germany.
authors.forename: George M
authors.initials: GM
authors.lastname: Sheldrick
authors.affiliation: School of Engineering, Physics and Mathematics, University of Dundee, Dundee DD1 4HN, UK. College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK. sc3210@gmail.com u.zachariae@dundee.ac.uk bgroot@gwdg.de.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Zachariae
authors.affiliation: Biomolecular Dynamics Group, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany. sc3210@gmail.com u.zachariae@dundee.ac.uk bgroot@gwdg.de.
authors.forename: Bert L
authors.initials: BL
authors.lastname: de Groot
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D018360:Crystallography, X-Ray; D056004:Molecular Dynamics Simulation; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D055672:Static Electricity; D014867:Water
chemical_list: D001426:Bacterial Proteins; D015221:Potassium Channels; C107790:prokaryotic potassium channel; D014867:Water; D011188:Potassium