1. Structural Biology and Molecular Biophysics
  2. Computational and Systems Biology

Precise assembly of complex beta sheet topologies from de novo designed building blocks

  1. Indigo Chris King  Is a corresponding author
  2. James Gleixner
  3. Lindsey Doyle
  4. Alexandre Kuzin
  5. John F Hunt
  6. Rong Xiao
  7. Gaetano T Montelione
  8. Barry L Stoddard
  9. Frank DiMaio
  10. David Baker
  1. University of Washington, United States
  2. Fred Hutchinson Cancer Research Center, United States
  3. Columbia University, United States
  4. Rutgers, The State University of New Jersey, United States
https://doi.org/10.7554/eLife.11012
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Cite this article
  1. Indigo Chris King
  2. James Gleixner
  3. Lindsey Doyle
  4. Alexandre Kuzin
  5. John F Hunt
  6. Rong Xiao
  7. Gaetano T Montelione
  8. Barry L Stoddard
  9. Frank DiMaio
  10. David Baker
(2015)
Precise assembly of complex beta sheet topologies from de novo designed building blocks
eLife 4:e11012.
https://doi.org/10.7554/eLife.11012
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Abstract

Design of complex alpha-beta protein topologies poses a challenge because of the large number of alternative packing arrangements. A similar challenge presumably limited the emergence of large and complex protein topologies in evolution. Here we demonstrate that protein topologies with six and seven-stranded beta sheets can be designed by insertion of one de novo designed beta sheet containing protein into another such that the two beta sheets are merged to form a single extended sheet, followed by amino acid sequence optimization at the newly formed strand-strand, strand-helix, and helix-helix interfaces. Crystal structures of two such designs closely match the computational design models. Searches for similar structures in the SCOP protein domain database yield only weak matches with different beta sheet connectivities. A similar beta sheet fusion mechanism may have contributed to the emergence of complex beta sheets during natural protein evolution.

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Author details

  1. Indigo Chris King

    Molecular Engineering and Sciences Building, University of Washington, Seattle, United States
    For correspondence
    chrisk1@uw.edu
    Competing interests
    The authors declare that no competing interests exist.

  2. James Gleixner

    Institute for Protein Design, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Lindsey Doyle

    Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Alexandre Kuzin

    Biological Sciences, Northeast Structural Genomics Consortium, Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. John F Hunt

    Biological Sciences, Northeast Structural Genomics Consortium, Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Rong Xiao

    Center for Advanced Biotechnology and Medicine, Department of Molecular Biology and Biochemistry, Northeast Structural Genomics Consortium, Rutgers, The State University of New Jersey, Piscataway, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. Gaetano T Montelione

    Center for Advanced Biotechnology and Medicine, Department of Molecular Biology and Biochemistry, Northeast Struc-tural Genomics Consortium, Rutgers, The State University of New Jersey, Piscataway, United States
    Competing interests
    The authors declare that no competing interests exist.

  8. Barry L Stoddard

    Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.

  9. Frank DiMaio

    Institute for Protein Design, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.

  10. David Baker

    Institute for Protein Design, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Nir Ben-Tal, Tel Aviv University, Israel

Version history

  1. Received: August 20, 2015
  2. Accepted: December 8, 2015
  3. Accepted Manuscript published: December 9, 2015 (version 1)
  4. Version of Record published: January 20, 2016 (version 2)

Copyright

© 2015, King 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. Indigo Chris King
  2. James Gleixner
  3. Lindsey Doyle
  4. Alexandre Kuzin
  5. John F Hunt
  6. Rong Xiao
  7. Gaetano T Montelione
  8. Barry L Stoddard
  9. Frank DiMaio
  10. David Baker
(2015)
Precise assembly of complex beta sheet topologies from de novo designed building blocks
eLife 4:e11012.
https://doi.org/10.7554/eLife.11012

Share this article

https://doi.org/10.7554/eLife.11012

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