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

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, understand...

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Autores principales: Wargacki, Adam J., Wörner, Tobias P., van de Waterbeemd, Michiel, Ellis, Daniel, Heck, Albert J. R., King, Neil P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873210/
https://www.ncbi.nlm.nih.gov/pubmed/33563988
http://dx.doi.org/10.1038/s41467-021-21251-y
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author Wargacki, Adam J.
Wörner, Tobias P.
van de Waterbeemd, Michiel
Ellis, Daniel
Heck, Albert J. R.
King, Neil P.
author_facet Wargacki, Adam J.
Wörner, Tobias P.
van de Waterbeemd, Michiel
Ellis, Daniel
Heck, Albert J. R.
King, Neil P.
author_sort Wargacki, Adam J.
collection PubMed
description 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.
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spelling pubmed-78732102021-02-16 Complete and cooperative in vitro assembly of computationally designed self-assembling protein nanomaterials Wargacki, Adam J. Wörner, Tobias P. van de Waterbeemd, Michiel Ellis, Daniel Heck, Albert J. R. King, Neil P. Nat Commun Article 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. Nature Publishing Group UK 2021-02-09 /pmc/articles/PMC7873210/ /pubmed/33563988 http://dx.doi.org/10.1038/s41467-021-21251-y Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Wargacki, Adam J.
Wörner, Tobias P.
van de Waterbeemd, Michiel
Ellis, Daniel
Heck, Albert J. R.
King, Neil P.
Complete and cooperative in vitro assembly of computationally designed self-assembling protein nanomaterials
title Complete and cooperative in vitro assembly of computationally designed self-assembling protein nanomaterials
title_full Complete and cooperative in vitro assembly of computationally designed self-assembling protein nanomaterials
title_fullStr Complete and cooperative in vitro assembly of computationally designed self-assembling protein nanomaterials
title_full_unstemmed Complete and cooperative in vitro assembly of computationally designed self-assembling protein nanomaterials
title_short Complete and cooperative in vitro assembly of computationally designed self-assembling protein nanomaterials
title_sort complete and cooperative in vitro assembly of computationally designed self-assembling protein nanomaterials
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873210/
https://www.ncbi.nlm.nih.gov/pubmed/33563988
http://dx.doi.org/10.1038/s41467-021-21251-y
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