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Complete and cooperative in vitro assembly of computationally designed self-assembling protein nanomaterials

Author

Listed:
  • Adam J. Wargacki

    (University of Washington
    University of Washington)

  • Tobias P. Wörner

    (Utrecht University)

  • Michiel Waterbeemd

    (Utrecht University)

  • Daniel Ellis

    (University of Washington
    University of Washington
    University of Washington)

  • Albert J. R. Heck

    (Utrecht University)

  • Neil P. King

    (University of Washington
    University of Washington)

Abstract

Recent advances in computational methods have enabled the predictive design of self-assembling protein nanomaterials with atomic-level accuracy. These design strategies focus exclusively on a single target structure, without consideration of the mechanism or dynamics of assembly. However, understanding the assembly process, and in particular its robustness to perturbation, will be critical for translating this class of materials into useful technologies. Here we investigate the assembly of two computationally designed, 120-subunit icosahedral complexes in detail using several complementary biochemical methods. We found that assembly of each material from its two constituent protein building blocks was highly cooperative and yielded exclusively complete, 120-subunit complexes except in one non-stoichiometric regime for one of the materials. Our results suggest that in vitro assembly provides a robust and controllable route for the manufacture of designed protein nanomaterials and confirm that cooperative assembly can be an intrinsic, rather than evolved, feature of hierarchically structured protein complexes.

Suggested Citation

  • Adam J. Wargacki & Tobias P. Wörner & Michiel Waterbeemd & Daniel Ellis & Albert J. R. Heck & Neil P. King, 2021. "Complete and cooperative in vitro assembly of computationally designed self-assembling protein nanomaterials," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21251-y
    DOI: 10.1038/s41467-021-21251-y
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    Cited by:

    1. Geoffrey B. Hutchinson & Olubukola M. Abiona & Cynthia T. Ziwawo & Anne P. Werner & Daniel Ellis & Yaroslav Tsybovsky & Sarah R. Leist & Charis Palandjian & Ande West & Ethan J. Fritch & Nianshuang Wa, 2023. "Nanoparticle display of prefusion coronavirus spike elicits S1-focused cross-reactive antibody response against diverse coronavirus subgenera," Nature Communications, Nature, vol. 14(1), pages 1-11, December.

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