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

Lai, Yen-Ting; Reading, Eamonn; Hura, Greg L.; Tsai, Kuang-Lei; Laganowsky, Arthur; Asturias, Francisco J.; Tainer, John A.; Robinson, Carol V.; Yeates, Todd O.

doi:10.1038/nchem.2107

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

Journal Article · Mon Nov 10 00:00:00 EST 2014 · Nature Chemistry

DOI:https://doi.org/10.1038/nchem.2107· OSTI ID:1164570

Lai, Yen-Ting ^[1]; Reading, Eamonn ^[2]; Hura, Greg L. ^[3]; Tsai, Kuang-Lei ^[4]; Laganowsky, Arthur ^[2]; Asturias, Francisco J. ^[4]; Tainer, John A. ^[5]; Robinson, Carol V. ^[2]; Yeates, Todd O. ^[6]

Univ. of California, Los Angeles, CA (United States). UCLA-DOE Institute for Genomics and Proteomics
Univ. of Oxford (United Kingdom). Dept of Chemistry
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Univ. of California, Santa Cruz, CA (United States)
Scripps Research Inst., La Jolla, FL (United States)
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Scripps Research Inst., La Jolla, FL (United States)
Univ. of California, Los Angeles, CA (United States). UCLA-DOE Institute for Genomics and Proteomics; Univ. of California, Los Angeles, CA (United States). Dept. of Chemistry and Biochemistry; Univ. of California, Los Angeles, CA (United States). California Nanosystems Institute

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 alternate assembly forms in solution. These studies show that accurate design of large porous assemblies with specific shapes is feasible, while further specificity improvements will likely require limiting flexibility to select against alternative forms. Finally, these results provide a foundation for the design of advanced materials with applications in bionanotechnology, nanomedicine and material sciences.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: AC02-05CH11231; CHE-1332907; R01GM067167

OSTI ID:: 1164570

Journal Information:: Nature Chemistry, Vol. 6, Issue 12; ISSN 1755-4330

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Cited by: 206 works

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