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

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.
Authors:
 [1] ;  [2] ;  [3] ;  [4] ;  [2] ;  [4] ;  [5] ;  [2] ;  [6]
  1. Univ. of California, Los Angeles, CA (United States). UCLA-DOE Institute for Genomics and Proteomics
  2. Univ. of Oxford (United Kingdom). Dept of Chemistry
  3. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Univ. of California, Santa Cruz, CA (United States)
  4. Scripps Research Inst., La Jolla, FL (United States)
  5. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Scripps Research Inst., La Jolla, FL (United States)
  6. 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
Publication Date:
OSTI Identifier:
1164570
Grant/Contract Number:
AC02-05CH11231; CHE-1332907; R01GM067167
Type:
Accepted Manuscript
Journal Name:
Nature Chemistry
Additional Journal Information:
Journal Volume: 6; Journal Issue: 12; Journal ID: ISSN 1755-4330
Publisher:
Nature Publishing Group
Research Org:
Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
Sponsoring Org:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES Porous protein nanoparticles; protein design; self-assembly; symmetry; synthetic biology and bioengineering