1. Biochemistry and Chemical Biology
  2. Structural Biology and Molecular Biophysics
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Conformational dynamics of the nucleotide binding domains and the power stroke of a heterodimeric ABC transporter

  1. Smriti Mishra
  2. Brandy Verhalen
  3. Richard A Stein
  4. Po-Chao Wen
  5. Emad Tajkhorshid
  6. Hassane S Mchaourab  Is a corresponding author
  1. Vanderbilt University, United States
  2. University of Illinois, United States
Research Article
  • Cited 77
  • Views 3,137
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Cite this article as: eLife 2014;3:e02740 doi: 10.7554/eLife.02740

Abstract

Multidrug ATP binding cassette (ABC) exporters are ubiquitous ABC transporters that extrude cytotoxic molecules across cell membranes. Despite recent progress in structure determination of these transporters, the conformational motion that transduces the energy of ATP hydrolysis to the work of substrate translocation remains undefined. Here, we have investigated the conformational cycle of BmrCD, a representative of the heterodimer family of ABC exporters that have an intrinsically impaired nucleotide binding site. We measured distances between pairs of spin labels monitoring the movement of the nucleotide binding (NBD) and transmembrane domains (TMD). The results expose previously unobserved structural intermediates of the NBDs arising from asymmetric configuration of catalytically inequivalent nucleotide binding sites. The two-state transition of the TMD, from an inward- to an outward-facing conformation, is driven exclusively by ATP hydrolysis. These findings provide direct evidence of divergence in the mechanism of ABC exporters.

Article and author information

Author details

  1. Smriti Mishra

    Vanderbilt University, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Brandy Verhalen

    Vanderbilt University, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Richard A Stein

    Vanderbilt University, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Po-Chao Wen

    University of Illinois, Urbana, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Emad Tajkhorshid

    University of Illinois, Urbana, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Hassane S Mchaourab

    Vanderbilt University, Nashville, United States
    For correspondence
    hassane.mchaourab@vanderbilt.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Volker Dötsch, Goethe University, Germany

Publication history

  1. Received: March 8, 2014
  2. Accepted: May 13, 2014
  3. Accepted Manuscript published: May 16, 2014 (version 1)
  4. Version of Record published: June 10, 2014 (version 2)

Copyright

© 2014, Mishra 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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