bMERB domains are bivalent Rab8 family effectors evolved by gene duplication

  1. Amrita Rai
  2. Anastasia Oprisko
  3. Jeremy Campos
  4. Yangxue Fu
  5. Timon Friese
  6. Aymelt Itzen
  7. Roger S Goody  Is a corresponding author
  8. Emerich Mihai Gazdag  Is a corresponding author
  9. Matthias P Müller  Is a corresponding author
  1. Max Planck Institute of Molecular Physiology, Germany
  2. Technische Universität München, Germany

Abstract

In their active GTP-bound form, Rab proteins interact with proteins termed effector molecules. In this study we have thoroughly characterised a Rab effector domain that is present in proteins of the Mical and EHBP families, both known to act in endosomal trafficking. Within our study, we show that these effectors display a preference for Rab8 family proteins (Rab8, 10, 13 and 15) and that some of the effector domains can bind two Rab proteins via separate binding sites. Structural analysis allowed us to explain the specificity towards Rab8 family members and the presence of two similar Rab binding sites that must have evolved via gene duplication. This study is the first to thoroughly characterise a Rab effector protein that contains two separate Rab binding sites within a single domain, allowing Micals and EHBPs to bind two Rabs simultaneously, thus suggesting previously unknown functions of these effector molecules in endosomal trafficking.

Article and author information

Author details

  1. Amrita Rai

    Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Anastasia Oprisko

    Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Jeremy Campos

    Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Yangxue Fu

    Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Timon Friese

    Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Aymelt Itzen

    Center for Integrated Protein Science Munich, Technische Universität München, Garching, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Roger S Goody

    Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany
    For correspondence
    goody@mpi-dortmund.mpg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0772-0444
  8. Emerich Mihai Gazdag

    Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany
    For correspondence
    emerich-mihai.gazdag@mpi-dortmund.mpg.de
    Competing interests
    The authors declare that no competing interests exist.
  9. Matthias P Müller

    Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany
    For correspondence
    matthias.mueller@mpi-dortmund.mpg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1529-8933

Funding

Max-Planck-Gesellschaft (No grant number)

  • Amrita Rai
  • Roger S Goody
  • Emerich Mihai Gazdag
  • Matthias P Müller

Deutsche Forschungsgemeinschaft (SFB642, project A4)

  • Roger S Goody
  • Matthias P Müller

Deutsche Forschungsgemeinschaft (SFB1035, project B05)

  • Aymelt Itzen

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Reinhard Jahn, Max Planck Institute for Biophysical Chemistry, Germany

Version history

  1. Received: June 10, 2016
  2. Accepted: August 22, 2016
  3. Accepted Manuscript published: August 23, 2016 (version 1)
  4. Accepted Manuscript updated: August 24, 2016 (version 2)
  5. Accepted Manuscript updated: August 25, 2016 (version 3)
  6. Version of Record published: September 16, 2016 (version 4)

Copyright

© 2016, Rai 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. Amrita Rai
  2. Anastasia Oprisko
  3. Jeremy Campos
  4. Yangxue Fu
  5. Timon Friese
  6. Aymelt Itzen
  7. Roger S Goody
  8. Emerich Mihai Gazdag
  9. Matthias P Müller
(2016)
bMERB domains are bivalent Rab8 family effectors evolved by gene duplication
eLife 5:e18675.
https://doi.org/10.7554/eLife.18675

Share this article

https://doi.org/10.7554/eLife.18675

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