1. Biochemistry and Chemical Biology
  2. Structural Biology and Molecular Biophysics
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Structure and substrate ion binding in the sodium/proton antiporter PaNhaP

  1. David Wöhlert
  2. Werner Kühlbrandt
  3. Özkan Yildiz  Is a corresponding author
  1. Max Planck Institute of Biophysics, Germany
Research Article
  • Cited 56
  • Views 2,150
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Cite this article as: eLife 2014;3:e03579 doi: 10.7554/eLife.03579
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Abstract

Sodium/proton antiporters maintain intracellular pH and sodium levels. Detailed structures of antiporters with bound substrate ions are essential for understanding how they work. We have resolved the substrate ion in the dimeric, electroneutral sodium/proton antiporter PaNhaP from Pyrococcus abyssi at 3.2 Å, and have determined its structure in two different conformations at pH8 and pH4. The ion is coordinated by three acidic sidechains, a water molecule, a serine and a main-chain carbonyl in the unwound stretch of trans-membrane helix 5 at the deepest point of a negatively charged cytoplasmic funnel. A second narrow polar channel may facilitate proton uptake from the cytoplasm. Transport activity of PaNhaP is cooperative at pH6 but not at pH5. Cooperativity is due to pH-dependent allosteric coupling of protomers through two histidines at the dimer interface. Combined with comprehensive transport studies, the structures of PaNhaP offer unique new insights into the transport mechanism of sodium/proton antiporters.

Article and author information

Author details

  1. David Wöhlert

    Max Planck Institute of Biophysics, Frankfurt am Main, Germany
    Competing interests
    No competing interests declared.
  2. Werner Kühlbrandt

    Max Planck Institute of Biophysics, Frankfurt am Main, Germany
    Competing interests
    Werner Kühlbrandt, Reviewing editor, eLife..
  3. Özkan Yildiz

    Max Planck Institute of Biophysics, Frankfurt am Main, Germany
    For correspondence
    Oezkan.Yildiz@biophys.mpg.de
    Competing interests
    No competing interests declared.

Reviewing Editor

  1. Richard Aldrich, The University of Texas at Austin, United States

Publication history

  1. Received: June 6, 2014
  2. Accepted: November 25, 2014
  3. Accepted Manuscript published: November 26, 2014 (version 1)
  4. Accepted Manuscript updated: November 28, 2014 (version 2)
  5. Version of Record published: December 16, 2014 (version 3)

Copyright

© 2014, Wöhlert et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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