1. Structural Biology and Molecular Biophysics
  2. Microbiology and Infectious Disease
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Structural basis for ligand and innate immunity factor uptake by the trypanosome haptoglobin-haemoglobin receptor

  1. Harriet Lane-Serff
  2. Paula MacGregor
  3. Edward Lowe
  4. Mark Carrington
  5. Matthew Higgins  Is a corresponding author
  1. University of Oxford, United Kingdom
  2. University of Cambridge, United Kingdom
Research Article
  • Cited 14
  • Views 2,142
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Cite this article as: eLife 2014;3:e05553 doi: 10.7554/eLife.05553

Abstract

The haptoglobin-haemoglobin receptor (HpHbR) of African trypanosomes allows acquisition of haem and provides an uptake route for trypanolytic factor-1, a mediator of innate immunity against trypanosome infection. Here we report the structure of Trypanosoma brucei HpHbR in complex with human haptoglobin-haemoglobin (HpHb), revealing an elongated ligand-binding site that extends along its membrane distal half. This contacts haptoglobin and the β-subunit of haemoglobin, showing how the receptor selectively binds HpHb over individual components. Lateral mobility of the glycosylphophatidylinositol-anchored HpHbR, and a ~50{degree sign} kink in the receptor, allows two receptors to simultaneously bind one HpHb dimer. Indeed, trypanosomes take up dimeric HpHb at significantly lower concentrations than monomeric HpHb, due to increased ligand avidity that comes from bivalent binding. The structure therefore reveals the molecular basis for ligand and innate immunity factor uptake by trypanosomes, and identifies adaptations that allow efficient ligand uptake in the context of the complex trypanosome cell surface.

Article and author information

Author details

  1. Harriet Lane-Serff

    Department of Biochemistry, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Paula MacGregor

    Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Edward Lowe

    Department of Biochemistry, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Mark Carrington

    Biochemistry, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Matthew Higgins

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

Reviewing Editor

  1. Volker Dötsch, Goethe University, Germany

Publication history

  1. Received: November 11, 2014
  2. Accepted: December 12, 2014
  3. Accepted Manuscript published: December 12, 2014 (version 1)
  4. Version of Record published: January 9, 2015 (version 2)

Copyright

© 2014, Lane-Serff 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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