1. Structural Biology and Molecular Biophysics
  2. Computational and Systems Biology
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Emergence and evolution of an interaction between intrinsically disordered proteins

  1. Greta Hultqvist  Is a corresponding author
  2. Emma Åberg
  3. Carlo Camilloni
  4. Gustav N Sundell
  5. Eva Andersson
  6. Jakob Dogan
  7. Celestine N chi
  8. Michele Vendruscolo  Is a corresponding author
  9. Per Jemth  Is a corresponding author
  1. Uppsala University, Sweden
  2. University of Cambridge, United Kingdom
  3. ETH Zürich, Switzerland
Research Article
  • Cited 18
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Cite this article as: eLife 2017;6:e16059 doi: 10.7554/eLife.16059

Abstract

Protein-protein interactions involving intrinsically disordered proteins are important for cellular function and common in all organisms. However, it is not clear how such interactions emerge and evolve on a molecular level. We performed phylogenetic reconstruction, resurrection and biophysical characterization of two interacting disordered protein domains, CID and NCBD. CID appeared after the divergence of protostomes and deuterostomes 450-600 million years ago, while NCBD was present in the protostome/deuterostome ancestor. The most ancient CID/NCBD formed a relatively weak complex (Kd~5 μM). At the time of the first vertebrate-specific whole genome duplication the affinity had increased (Kd~200 nM) and was maintained in further speciation. Experiments together with molecular modeling using NMR chemical shifts suggest that new interactions involving intrinsically disordered proteins may evolve via a low affinity complex which is optimized by modulating direct interactions as well as dynamics, while tolerating several potentially disruptive mutations.

Article and author information

Author details

  1. Greta Hultqvist

    Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden
    For correspondence
    greta.hultqvist@pubcare.uu.se
    Competing interests
    The authors declare that no competing interests exist.
  2. Emma Åberg

    Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  3. Carlo Camilloni

    Department of Chemistry, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Gustav N Sundell

    Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  5. Eva Andersson

    Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  6. Jakob Dogan

    Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  7. Celestine N chi

    Laboratory of Physical Chemistry, ETH Zürich, Zürich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4154-2378
  8. Michele Vendruscolo

    Department of Chemistry, University of Cambridge, Cambridge, United Kingdom
    For correspondence
    mv245@cam.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3616-1610
  9. Per Jemth

    Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden
    For correspondence
    Per.Jemth@imbim.uu.se
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1516-7228

Funding

Vetenskapsrådet

  • Per Jemth

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

Reviewing Editor

  1. Jeffery W Kelly, The Scripps Research Institute, United States

Publication history

  1. Received: March 15, 2016
  2. Accepted: March 28, 2017
  3. Accepted Manuscript published: April 11, 2017 (version 1)
  4. Version of Record published: May 5, 2017 (version 2)
  5. Version of Record updated: February 12, 2018 (version 3)

Copyright

© 2017, Hultqvist 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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