Guanylate binding proteins (GBPs) directly attack T. gondii via supramolecular complexes

  1. Elisabeth Kravets
  2. Daniel Degrandi
  3. Qijun Ma
  4. Thomas-Otavio Peulen
  5. Verena Klümpers
  6. Suren Felekyan
  7. Ralf Kühnemuth
  8. Stefanie Weidtkamp-Peters
  9. Claus AM Seidel  Is a corresponding author
  10. Klaus Pfeffer
  1. Heinrich-Heine University Düsseldorf, Germany
  2. Heinrich-Heine-University Düsseldorf, Germany
  3. Heidelberg University, Germany

Abstract

GBPs are essential for immunity against intracellular pathogens, especially for T. gondii control. Here, the molecular interactions of murine GBPs (mGBP1/2/3/5/6), homo- and hetero-multimerization properties of mGBP2 and its function in parasite killing were investigated by mutational, Multiparameter Fluorescence Image Spectroscopy, and live cell microscopy methodologies. Control of T. gondii replication by mGBP2 requires GTP hydrolysis and isoprenylation thus, enabling reversible oligomerization in vesicle-like structures. mGBP2 undergoes structural transitions between monomeric, dimeric and oligomeric states visualized by quantitative FRET analysis. mGBPs reside in at least two discrete subcellular reservoirs and attack the parasitophorous vacuole membrane (PVM) as orchestrated, supramolecular complexes forming large, densely packed multimers comprising up to several thousand monomers. This dramatic mGBP enrichment results in the loss of PVM integrity, followed by a direct assault of mGBP2 upon the plasma membrane of the parasite. These discoveries provide vital dynamic and molecular perceptions into cell-autonomous immunity.

Article and author information

Author details

  1. Elisabeth Kravets

    Institute of Medical Microbiology and Hospital Hygiene, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Daniel Degrandi

    Institute of Medical Microbiology and Hospital Hygiene, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Qijun Ma

    Institute for Molecular Physical Chemistry, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Thomas-Otavio Peulen

    Institute for Molecular Physical Chemistry, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Verena Klümpers

    Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Suren Felekyan

    Institute for Molecular Physical Chemistry, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Ralf Kühnemuth

    Institute for Molecular Physical Chemistry, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
    Competing interests
    The authors declare that no competing interests exist.
  8. Stefanie Weidtkamp-Peters

    Center of Advanced Imaging, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
    Competing interests
    The authors declare that no competing interests exist.
  9. Claus AM Seidel

    Institute for Molecular Physical Chemistry, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
    For correspondence
    cseidel@hhu.de
    Competing interests
    The authors declare that no competing interests exist.
  10. Klaus Pfeffer

    Institute of Medical Microbiology and Hospital Hygiene, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Taekjip Ha, Johns Hopkins University School of Medicine, United States

Version history

  1. Received: September 9, 2015
  2. Accepted: January 26, 2016
  3. Accepted Manuscript published: January 27, 2016 (version 1)
  4. Version of Record published: February 29, 2016 (version 2)

Copyright

© 2016, Kravets 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. Elisabeth Kravets
  2. Daniel Degrandi
  3. Qijun Ma
  4. Thomas-Otavio Peulen
  5. Verena Klümpers
  6. Suren Felekyan
  7. Ralf Kühnemuth
  8. Stefanie Weidtkamp-Peters
  9. Claus AM Seidel
  10. Klaus Pfeffer
(2016)
Guanylate binding proteins (GBPs) directly attack T. gondii via supramolecular complexes
eLife 5:e11479.
https://doi.org/10.7554/eLife.11479

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