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Accurate design of co-assembling multi-component protein nanomaterials

Author

Listed:
  • Neil P. King

    (University of Washington
    Institute for Protein Design, University of Washington)

  • Jacob B. Bale

    (University of Washington
    Graduate Program in Molecular and Cellular Biology, University of Washington)

  • William Sheffler

    (University of Washington)

  • Dan E. McNamara

    (UCLA Department of Chemistry and Biochemistry)

  • Shane Gonen

    (University of Washington
    Janelia Farm Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, Virginia 20147, USA)

  • Tamir Gonen

    (Janelia Farm Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, Virginia 20147, USA)

  • Todd O. Yeates

    (UCLA Department of Chemistry and Biochemistry
    UCLA-DOE Institute for Genomics and Proteomics
    UCLA Molecular Biology Institute)

  • David Baker

    (University of Washington
    Institute for Protein Design, University of Washington
    Howard Hughes Medical Institute, University of Washington)

Abstract

The self-assembly of proteins into highly ordered nanoscale architectures is a hallmark of biological systems. The sophisticated functions of these molecular machines have inspired the development of methods to engineer self-assembling protein nanostructures; however, the design of multi-component protein nanomaterials with high accuracy remains an outstanding challenge. Here we report a computational method for designing protein nanomaterials in which multiple copies of two distinct subunits co-assemble into a specific architecture. We use the method to design five 24-subunit cage-like protein nanomaterials in two distinct symmetric architectures and experimentally demonstrate that their structures are in close agreement with the computational design models. The accuracy of the method and the number and variety of two-component materials that it makes accessible suggest a route to the construction of functional protein nanomaterials tailored to specific applications.

Suggested Citation

  • Neil P. King & Jacob B. Bale & William Sheffler & Dan E. McNamara & Shane Gonen & Tamir Gonen & Todd O. Yeates & David Baker, 2014. "Accurate design of co-assembling multi-component protein nanomaterials," Nature, Nature, vol. 510(7503), pages 103-108, June.
  • Handle: RePEc:nat:nature:v:510:y:2014:i:7503:d:10.1038_nature13404
    DOI: 10.1038/nature13404
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    Cited by:

    1. Yin-Feng Kang & Cong Sun & Jing Sun & Chu Xie & Zhen Zhuang & Hui-Qin Xu & Zheng Liu & Yi-Hao Liu & Sui Peng & Run-Yu Yuan & Jin-Cun Zhao & Mu-Sheng Zeng, 2022. "Quadrivalent mosaic HexaPro-bearing nanoparticle vaccine protects against infection of SARS-CoV-2 variants," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    2. Rebecca F Alford & Andrew Leaver-Fay & Lynda Gonzales & Erin L Dolan & Jeffrey J Gray, 2017. "A cyber-linked undergraduate research experience in computational biomolecular structure prediction and design," PLOS Computational Biology, Public Library of Science, vol. 13(12), pages 1-13, December.

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