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Nat Chem. 2014 Dec;6(12):1065-71. doi: 10.1038/nchem.2107. Epub 2014 Nov 10.

Structure of a designed protein cage that self-assembles into a highly porous cube.

Author information

1
UCLA-DOE Institute for Genomics and Proteomics, University of California, Los Angeles, California 90095, USA.
2
Department of Chemistry, University of Oxford, Oxford OX1 3QZ, UK.
3
1] Lawrence Berkeley National Laboratory, Berkeley, California 94704, USA [2] Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, USA.
4
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
5
1] Lawrence Berkeley National Laboratory, Berkeley, California 94704, USA [2] Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California 92037, USA [3] The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
6
1] UCLA-DOE Institute for Genomics and Proteomics, University of California, Los Angeles, California 90095, USA [2] Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095-1569 USA [3] California Nanosystems Institute, University of California, Los Angeles, California 90095, USA.

Abstract

Natural proteins can be versatile building blocks for multimeric, self-assembling structures. Yet, creating protein-based assemblies with specific geometries and chemical properties remains challenging. Highly porous materials represent particularly interesting targets for designed assembly. Here, we utilize a strategy of fusing two natural protein oligomers using a continuous alpha-helical linker to design a novel protein that self assembles into a 750 kDa, 225 Å diameter, cube-shaped cage with large openings into a 130 Å diameter inner cavity. A crystal structure of the cage showed atomic-level agreement with the designed model, while electron microscopy, native mass spectrometry and small angle X-ray scattering revealed alternative assembly forms in solution. These studies show that accurate design of large porous assemblies with specific shapes is feasible, while further specificity improvements will probably require limiting flexibility to select against alternative forms. These results provide a foundation for the design of advanced materials with applications in bionanotechnology, nanomedicine and material sciences.

PMID:
25411884
PMCID:
PMC4239666
DOI:
10.1038/nchem.2107
[Indexed for MEDLINE]
Free PMC Article
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