Molecular determinants of permeation in a fluoride-specific ion channel

  1. Nicholas B Last
  2. Senmiao Sun
  3. Minh C Pham
  4. Christopher Miller  Is a corresponding author
  1. Howard Hughes Medical Institute, Brandeis University, United States

Abstract

Fluoride ion channels of the Fluc family combat toxicity arising from accumulation of environmental F-. Although crystal structures are known, the densely packed pore region has precluded delineation of the ion pathway. Here we chart out the Fluc pore and characterize its chemical requirements for transport. A ladder of H-bond donating residues creates a 'polar track' demarking the ion-conduction pathway. Surprisingly, while track polarity is well conserved, polarity is nonetheless functionally dispensable at several positions. A threonine at one end of the pore engages in vital interactions through its β-branched methyl group. Two critical central phenylalanines that directly coordinate F- through a quadrupolar-ion interaction cannot be functionally substituted by aromatic, non-polar, or polar sidechains. The only functional replacement is methionine, which coordinates F- through its partially positive γ-methylene in mimicry of phenylalanine's quadrupolar interaction. These results demonstrate the unusual chemical requirements for selectively transporting the strongly H-bonding F- anion.

Article and author information

Author details

  1. Nicholas B Last

    Department of Biochemistry, Howard Hughes Medical Institute, Brandeis University, Waltham, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Senmiao Sun

    Department of Biochemistry, Howard Hughes Medical Institute, Brandeis University, Waltham, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Minh C Pham

    Department of Biochemistry, Howard Hughes Medical Institute, Brandeis University, Waltham, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Christopher Miller

    Department of Biochemistry, Howard Hughes Medical Institute, Brandeis University, Waltham, United States
    For correspondence
    cmiller@brandeis.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0273-8653

Funding

Howard Hughes Medical Institute

  • Nicholas B Last
  • Christopher Miller

National Institute of General Medical Sciences (NIH GM107023)

  • Senmiao Sun
  • Minh C Pham

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Baron Chanda, University of Wisconsin-Madison, United States

Publication history

  1. Received: August 16, 2017
  2. Accepted: September 26, 2017
  3. Accepted Manuscript published: September 27, 2017 (version 1)
  4. Version of Record published: October 11, 2017 (version 2)

Copyright

© 2017, Last 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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  1. Nicholas B Last
  2. Senmiao Sun
  3. Minh C Pham
  4. Christopher Miller
(2017)
Molecular determinants of permeation in a fluoride-specific ion channel
eLife 6:e31259.
https://doi.org/10.7554/eLife.31259

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