Origin of a folded repeat protein from an intrinsically disordered ancestor

  1. Hongbo Zhu
  2. Edgardo Sepulveda
  3. Marcus D Hartmann
  4. Manjunatha Kogenaru
  5. Astrid Ursinus
  6. Eva Sulz
  7. Reinhard Albrecht
  8. Murray Coles
  9. Jörg Martin
  10. Andrei N Lupas  Is a corresponding author
  1. Max Planck Institute for Developmental Biology, Germany
  2. Imperial College London, United Kingdom

Abstract

Repetitive proteins are thought to have arisen through the amplification of subdomain-sized peptides. Many of these originated in a non-repetitive context as cofactors of RNA-based replication and catalysis, and required the RNA to assume their active conformation. In search of the origins of one of the most widespread repeat protein families, the tetratricopeptide repeat (TPR), we identified several potential homologs of its repeated helical hairpin in non-repetitive proteins, including the putatively ancient ribosomal protein S20 (RPS20), which only becomes structured in the context of the ribosome. We evaluated the ability of the RPS20 hairpin to form a TPR fold by amplification and obtained structures identical to natural TPRs for variants with 2-5 point mutations per repeat. The mutations were neutral in the parent organism, suggesting that they could have been sampled in the course of evolution. TPRs could thus have plausibly arisen by amplification from an ancestral helical hairpin.

Article and author information

Author details

  1. Hongbo Zhu

    Department of Protein Evolution, Max Planck Institute for Developmental Biology, Tübingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Edgardo Sepulveda

    Department of Protein Evolution, Max Planck Institute for Developmental Biology, Tübingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2413-8261
  3. Marcus D Hartmann

    Department of Protein Evolution, Max Planck Institute for Developmental Biology, Tübingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6937-5677
  4. Manjunatha Kogenaru

    Department of Life Sciences, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6570-7857
  5. Astrid Ursinus

    Department of Protein Evolution, Max Planck Institute for Developmental Biology, Tübingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Eva Sulz

    Department of Protein Evolution, Max Planck Institute for Developmental Biology, Tübingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Reinhard Albrecht

    Department of Protein Evolution, Max Planck Institute for Developmental Biology, Tübingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  8. Murray Coles

    Department of Protein Evolution, Max Planck Institute for Developmental Biology, Tübingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  9. Jörg Martin

    Department of Protein Evolution, Max Planck Institute for Developmental Biology, Tübingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  10. Andrei N Lupas

    Department of Protein Evolution, Max Planck Institute for Developmental Biology, Tübingen, Germany
    For correspondence
    andrei.lupas@tuebingen.mpg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1959-4836

Funding

Max-Planck-Gesellschaft

  • Hongbo Zhu
  • Edgardo Sepulveda
  • Marcus D Hartmann
  • Manjunatha Kogenaru
  • Astrid Ursinus
  • Eva Sulz
  • Reinhard Albrecht
  • Murray Coles
  • Jörg Martin
  • Andrei N Lupas

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

Copyright

© 2016, Zhu 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. Hongbo Zhu
  2. Edgardo Sepulveda
  3. Marcus D Hartmann
  4. Manjunatha Kogenaru
  5. Astrid Ursinus
  6. Eva Sulz
  7. Reinhard Albrecht
  8. Murray Coles
  9. Jörg Martin
  10. Andrei N Lupas
(2016)
Origin of a folded repeat protein from an intrinsically disordered ancestor
eLife 5:e16761.
https://doi.org/10.7554/eLife.16761

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https://doi.org/10.7554/eLife.16761