1. Structural Biology and Molecular Biophysics
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Allosteric signalling in the outer membrane translocation domain of PapC usher

  1. Irene Farabella
  2. Thieng Pham
  3. Nadine S Henderson
  4. Sebastian Geibel
  5. Gilles Phan
  6. David G Thanassi
  7. Anne H Delcour
  8. Gabriel Waksman
  9. Maya Topf  Is a corresponding author
  1. Birkbeck College, United Kingdom
  2. University of Houston, United States
  3. Stony Brook University, United States
  4. University of Würzburg, Germany
  5. Université Paris Descartes, France
Research Article
  • Cited 14
  • Views 1,644
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Cite this article as: eLife 2014;3:e03532 doi: 10.7554/eLife.03532

Abstract

PapC ushers are outer-membrane proteins enabling assembly and secretion of P pili in uropathogenic E. coli. Their translocation domain is a large β-barrel occluded by a plug domain, which is displaced to allow the translocation of pilus subunits across the membrane. Previous studies suggested that this gating mechanism is controlled by a β-hairpin and an α-helix. To investigate the role of these elements in allosteric signal communication we developed a method combining evolutionary and molecular dynamics studies of the native translocation domain and mutants lacking the β-hairpin and/or α-helix. Analysis of a hybrid residue interaction network suggests distinct regions (residue 'communities') within the translocation domain (especially around β12-β14) linking these elements, thereby modulating PapC gating. Antibiotic sensitivity and electrophysiology experiments on a set of alanine-substitution mutants confirmed functional roles for four of these communities. This study illuminates the gating mechanism of PapC ushers and its importance in maintaining outer-membrane permeability.

Article and author information

Author details

  1. Irene Farabella

    Birkbeck College, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Thieng Pham

    University of Houston, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Nadine S Henderson

    Stony Brook University, Stony Brook, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Sebastian Geibel

    University of Würzburg, Würzburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Gilles Phan

    Université Paris Descartes, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  6. David G Thanassi

    Stony Brook University, Stony Brook, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Anne H Delcour

    University of Houston, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Gabriel Waksman

    Birkbeck College, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  9. Maya Topf

    Birkbeck College, London, United Kingdom
    For correspondence
    m.topf@mail.cryst.bbk.ac.uk
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Volker Dötsch, Goethe University, Germany

Publication history

  1. Received: May 30, 2014
  2. Accepted: September 29, 2014
  3. Accepted Manuscript published: October 1, 2014 (version 1)
  4. Version of Record published: October 28, 2014 (version 2)
  5. Version of Record updated: September 27, 2016 (version 3)

Copyright

© 2014, Farabella 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. Further reading

Further reading

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    2. Structural Biology and Molecular Biophysics
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