1. Biochemistry and Chemical Biology
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One transporter, two mechanisms. Thermodynamic evidence for a dual transport mechanism in a POT family peptide transporter.

  1. Joanne L Parker
  2. Joseph A Mindell
  3. Simon Newstead  Is a corresponding author
  1. University of Oxford, United Kingdom
  2. National Institutes of Health, United States
Research Article
  • Cited 29
  • Views 2,469
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Cite this article as: eLife 2014;3:e04273 doi: 10.7554/eLife.04273

Abstract

Peptide transport plays an important role in cellular homeostasis as a key route for nitrogen acquisition in mammalian cells. PepT1 and PepT2, the mammalian proton coupled peptide transporters (POTs), function to assimilate and retain diet-derived peptides and play important roles in drug pharmacokinetics. A key characteristic of the POT family is the mechanism of peptide selectivity, with members able to recognise and transport > 8000 different peptides. Here we present thermodynamic evidence that in the bacterial POT family transporter PepTSt, from Streptococcus thermophilus, at least two alternative transport mechanisms operate to move peptides into the cell. Whilst tri-peptides are transported with a proton:peptide stoichiometry of 3:1, di-peptides are co-transported with either 4 or 5 protons. This is the first thermodynamic study of proton:peptide stoichiometry in the POT family and reveals that secondary active transporters can evolve different coupling mechanisms to accommodate and transport chemically and physically diverse ligands across the membrane.

Article and author information

Author details

  1. Joanne L Parker

    Department of Biochemistry, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Joseph A Mindell

    Membrane Transport Biophysics Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Simon Newstead

    Department of Biochemistry, University of Oxford, Oxford, United Kingdom
    For correspondence
    simon.newstead@bioch.ox.ac.uk
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. John Kuriyan, Howard Hughes Medical Institute, University of California, Berkeley, United States

Publication history

  1. Received: August 7, 2014
  2. Accepted: December 1, 2014
  3. Accepted Manuscript published: December 2, 2014 (version 1)
  4. Version of Record published: December 22, 2014 (version 2)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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