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Nature. 2014 Jun 5;510(7503):103-8. doi: 10.1038/nature13404. Epub 2014 May 25.

Accurate design of co-assembling multi-component protein nanomaterials.

Author information

1
1] Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA [2] Institute for Protein Design, University of Washington, Seattle, Washington 98195, USA [3].
2
1] Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA [2] Graduate Program in Molecular and Cellular Biology, University of Washington, Seattle, Washington 98195, USA [3].
3
1] Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA [2].
4
UCLA Department of Chemistry and Biochemistry, Los Angeles, California 90095, USA.
5
1] Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA [2] Janelia Farm Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, Virginia 20147, USA.
6
Janelia Farm Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, Virginia 20147, USA.
7
1] UCLA Department of Chemistry and Biochemistry, Los Angeles, California 90095, USA [2] UCLA-DOE Institute for Genomics and Proteomics, Los Angeles, California 90095, USA [3] UCLA Molecular Biology Institute, Los Angeles, California 90095, USA.
8
1] Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA [2] Institute for Protein Design, University of Washington, Seattle, Washington 98195, USA [3] Howard Hughes Medical Institute, University of Washington, Seattle, Washington 98195, USA.

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.

PMID:
24870237
PMCID:
PMC4137318
DOI:
10.1038/nature13404
[Indexed for MEDLINE]
Free PMC Article

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