15
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      The conduction pathway of potassium channels is water free under physiological conditions

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Detection of bound water in a potassium channel by solid-state NMR supports the “direct” knock-on ion permeation mechanism.

          Abstract

          Ion conduction through potassium channels is a fundamental process of life. On the basis of crystallographic data, it was originally proposed that potassium ions and water molecules are transported through the selectivity filter in an alternating arrangement, suggesting a “water-mediated” knock-on mechanism. Later on, this view was challenged by results from molecular dynamics simulations that revealed a “direct” knock-on mechanism where ions are in direct contact. Using solid-state nuclear magnetic resonance techniques tailored to characterize the interaction between water molecules and the ion channel, we show here that the selectivity filter of a potassium channel is free of water under physiological conditions. Our results are fully consistent with the direct knock-on mechanism of ion conduction but contradict the previously proposed water-mediated knock-on mechanism.

          Related collections

          Most cited references29

          • Record: found
          • Abstract: found
          • Article: found
          Is Open Access

          NMRFAM-SPARKY: enhanced software for biomolecular NMR spectroscopy

          Summary: SPARKY (Goddard and Kneller, SPARKY 3) remains the most popular software program for NMR data analysis, despite the fact that development of the package by its originators ceased in 2001. We have taken over the development of this package and describe NMRFAM-SPARKY, which implements new functions reflecting advances in the biomolecular NMR field. NMRFAM-SPARKY has been repackaged with current versions of Python and Tcl/Tk, which support new tools for NMR peak simulation and graphical assignment determination. These tools, along with chemical shift predictions from the PACSY database, greatly accelerate protein side chain assignments. NMRFAM-SPARKY supports automated data format interconversion for interfacing with a variety of web servers including, PECAN , PINE, TALOS-N, CS-Rosetta, SHIFTX2 and PONDEROSA-C/S. Availability and implementation: The software package, along with binary and source codes, if desired, can be downloaded freely from http://pine.nmrfam.wisc.edu/download_packages.html. Instruction manuals and video tutorials can be found at http://www.nmrfam.wisc.edu/nmrfam-sparky-distribution.htm. Contact: whlee@nmrfam.wisc.edu or markley@nmrfam.wisc.edu Supplementary information: Supplementary data are available at Bioinformatics online.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

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

            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.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Insight into the mechanism of the influenza A proton channel from a structure in a lipid bilayer.

              The M2 protein from the influenza A virus, an acid-activated proton-selective channel, has been the subject of numerous conductance, structural, and computational studies. However, little is known at the atomic level about the heart of the functional mechanism for this tetrameric protein, a His(37)-Trp(41) cluster. We report the structure of the M2 conductance domain (residues 22 to 62) in a lipid bilayer, which displays the defining features of the native protein that have not been attainable from structures solubilized by detergents. We propose that the tetrameric His(37)-Trp(41) cluster guides protons through the channel by forming and breaking hydrogen bonds between adjacent pairs of histidines and through specific interactions of the histidines with the tryptophan gate. This mechanism explains the main observations on M2 proton conductance.
                Bookmark

                Author and article information

                Journal
                Sci Adv
                Sci Adv
                SciAdv
                advances
                Science Advances
                American Association for the Advancement of Science
                2375-2548
                July 2019
                31 July 2019
                : 5
                : 7
                : eaaw6756
                Affiliations
                [1 ]Department of Molecular Biophysics, Leibniz-Forschungsinstitut für Molekulare Pharmakologie, 13125 Berlin, Germany.
                [2 ]Biomolecular Dynamics Group, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany.
                [3 ]Section Structural Biology, Leibniz-Forschungsinstitut für Molekulare Pharmakologie, 13125 Berlin, Germany.
                [4 ]Institut für Biologie, Humboldt-Universität zu Berlin, 10115 Berlin, Germany.
                Author notes
                [*]

                These authors contributed equally to this work.

                []Corresponding author. Email: alange@ 123456fmp-berlin.de
                Author information
                http://orcid.org/0000-0002-8723-4533
                http://orcid.org/0000-0003-4168-1706
                http://orcid.org/0000-0001-8801-9563
                http://orcid.org/0000-0002-1655-0838
                http://orcid.org/0000-0003-3570-3534
                http://orcid.org/0000-0002-7534-5973
                Article
                aaw6756
                10.1126/sciadv.aaw6756
                6669007
                31392272
                f35baee3-27ed-4791-9c81-b7466ab9f9b1
                Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

                This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

                History
                : 15 January 2019
                : 21 June 2019
                Funding
                Funded by: doi http://dx.doi.org/10.13039/501100000781, European Research Council;
                Award ID: 337490
                Categories
                Research Article
                Research Articles
                SciAdv r-articles
                Biophysics
                Custom metadata
                Sam Ardiente

                Comments

                Comment on this article