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Design of multi-scale protein complexes by hierarchical building block fusion

Author

Listed:
  • Yang Hsia

    (University of Washington
    University of Washington
    University of Washington)

  • Rubul Mout

    (University of Washington
    University of Washington)

  • William Sheffler

    (University of Washington
    University of Washington)

  • Natasha I. Edman

    (University of Washington
    University of Washington
    University of Washington
    University of Washington)

  • Ivan Vulovic

    (University of Washington
    University of Washington
    University of Washington)

  • Young-Jun Park

    (University of Washington)

  • Rachel L. Redler

    (New York University School of Medicine)

  • Matthew J. Bick

    (University of Washington
    University of Washington)

  • Asim K. Bera

    (University of Washington
    University of Washington)

  • Alexis Courbet

    (University of Washington
    University of Washington)

  • Alex Kang

    (University of Washington
    University of Washington)

  • T. J. Brunette

    (University of Washington
    University of Washington)

  • Una Nattermann

    (University of Washington
    University of Washington
    University of Washington)

  • Evelyn Tsai

    (University of Washington
    University of Washington)

  • Ayesha Saleem

    (University of Washington
    University of Washington)

  • Cameron M. Chow

    (University of Washington
    University of Washington)

  • Damian Ekiert

    (New York University School of Medicine
    New York University School of Medicine)

  • Gira Bhabha

    (New York University School of Medicine)

  • David Veesler

    (University of Washington)

  • David Baker

    (University of Washington
    University of Washington
    University of Washington)

Abstract

A systematic and robust approach to generating complex protein nanomaterials would have broad utility. We develop a hierarchical approach to designing multi-component protein assemblies from two classes of modular building blocks: designed helical repeat proteins (DHRs) and helical bundle oligomers (HBs). We first rigidly fuse DHRs to HBs to generate a large library of oligomeric building blocks. We then generate assemblies with cyclic, dihedral, and point group symmetries from these building blocks using architecture guided rigid helical fusion with new software named WORMS. X-ray crystallography and cryo-electron microscopy characterization show that the hierarchical design approach can accurately generate a wide range of assemblies, including a 43 nm diameter icosahedral nanocage. The computational methods and building block sets described here provide a very general route to de novo designed protein nanomaterials.

Suggested Citation

  • Yang Hsia & Rubul Mout & William Sheffler & Natasha I. Edman & Ivan Vulovic & Young-Jun Park & Rachel L. Redler & Matthew J. Bick & Asim K. Bera & Alexis Courbet & Alex Kang & T. J. Brunette & Una Nat, 2021. "Design of multi-scale protein complexes by hierarchical building block fusion," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22276-z
    DOI: 10.1038/s41467-021-22276-z
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    Cited by:

    1. Fatima A. Davila-Hernandez & Biao Jin & Harley Pyles & Shuai Zhang & Zheming Wang & Timothy F. Huddy & Asim K. Bera & Alex Kang & Chun-Long Chen & James J. Yoreo & David Baker, 2023. "Directing polymorph specific calcium carbonate formation with de novo protein templates," Nature Communications, Nature, vol. 14(1), pages 1-11, December.

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