1. Structural Biology and Molecular Biophysics
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Structure of the CLC-1 chloride channel from Homo sapiens

  1. Eunyong Park
  2. Roderick MacKinnon  Is a corresponding author
  1. The Rockefeller University, United States
Research Article
  • Cited 9
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Cite this article as: eLife 2018;7:e36629 doi: 10.7554/eLife.36629

Abstract

CLC channels mediate passive Cl- conduction, while CLC transporters mediate active Cl- transport coupled to H+ transport in the opposite direction. The distinction between CLC-0/1/2 channels and CLC transporters seems undetectable by amino acid sequence. To understand why they are different functionally we determined the structure of the human CLC-1 channel. Its 'glutamate gate' residue, known to mediate proton transfer in CLC transporters, adopts a location in the structure that appears to preclude it from its transport function. Furthermore, smaller side chains produce a wider pore near the intracellular surface, potentially reducing a kinetic barrier for Cl- conduction. When the corresponding residues are mutated in a transporter, it is converted to a channel. Finally, Cl- at key sites in the pore appear to interact with reduced affinity compared to transporters. Thus, subtle differences in glutamate gate conformation, internal pore diameter and Cl- affinity distinguish CLC channels and transporters.

Article and author information

Author details

  1. Eunyong Park

    Laboratory of Molecular Neurobiology and Biophysics, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Roderick MacKinnon

    Laboratory of Molecular Neurobiology and Biophysics, The Rockefeller University, New York, United States
    For correspondence
    mackinn@mail.rockefeller.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7605-4679

Funding

Howard Hughes Medical Institute

  • Roderick MacKinnon

Jane Coffin Childs Memorial Fund for Medical Research

  • Eunyong Park

Charles H. Revson Foundation

  • Eunyong Park

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

Reviewing Editor

  1. László Csanády, Semmelweis University, Hungary

Publication history

  1. Received: March 13, 2018
  2. Accepted: May 15, 2018
  3. Accepted Manuscript published: May 29, 2018 (version 1)
  4. Version of Record published: June 26, 2018 (version 2)

Copyright

© 2018, Park & MacKinnon

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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