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Generation of protein lattices by fusing proteins with matching rotational symmetry

Nature Nanotechnology volume 6, pages 558–562 (2011)Cite this article

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Abstract

The self-assembly of supramolecular structures that are ordered on the nanometre scale is a key objective in nanotechnology. DNA1,2,3,4 and peptide5,6,7 nanotechnologies have produced various two- and three-dimensional structures, but protein molecules have been underexploited in this area of research. Here we show that the genetic fusion of subunits from protein assemblies that have matching rotational symmetry generates species that can self-assemble into well-ordered, pre-determined one- and two-dimensional arrays that are stabilized by extensive intermolecular interactions. This new class of supramolecular structure provides a way to manufacture biomaterials with diverse structural and functional properties.

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Figure 1: Design of representative classes of crysalins.
Figure 2: Representative examples of 1D and 2D crysalins.
Figure 3: Comparison of the observed and designed projection maps of a crysalin.

References

  1. Rothemund, P. W. K. Folding DNA to create nanoscale shapes and patterns. Nature 440, 297–302 (2006).

    Article  CAS  Google Scholar 

  2. Douglas, S. M. et al. Self-assembly of DNA into nanoscale three-dimensional shapes. Nature 459, 414–418 (2009).

    Article  CAS  Google Scholar 

  3. Winfree, E., Liu, F. R., Wenzler, L. A. & Seeman, N. C. Design and self-assembly of two-dimensional DNA crystals. Nature 394, 539–544 (1998).

    Article  CAS  Google Scholar 

  4. Zheng, J. et al. From molecular to macroscopic via the rational design of a self-assembled 3D DNA crystal. Nature 461, 74–77 (2009).

    Article  CAS  Google Scholar 

  5. Rajagopal, K. & Schneider, J. P. Self-assembling peptides and proteins for nanotechnological applications. Curr. Opin. Struct. Biol. 14, 480–486 (2004).

    Article  CAS  Google Scholar 

  6. Colombo, G., Soto, P. & Gazit, E. Peptide self-assembly at the nanoscale: a challenging target for computational and experimental biotechnology. Trends Biotechnol. 25, 211–218 (2007).

    Article  CAS  Google Scholar 

  7. Woolfson, D. N. & Mahmoud, Z. N. More than just bare scaffolds: towards multi-component and decorated fibrous biomaterials. Chem. Soc. Rev. 39, 3464–3479 (2010).

    Article  CAS  Google Scholar 

  8. Zhang, S. Fabrication of novel biomaterials through molecular self-assembly. Nature Biotechnol. 21, 1171–1178 (2003).

    Article  CAS  Google Scholar 

  9. Moll, D. et al. S-layer-streptavidin fusion proteins as template for nanopatterned molecular arrays. Proc. Natl Acad. Sci. USA 99, 14646–14651 (2002).

    Article  CAS  Google Scholar 

  10. Sleytr, U. B., Egelseer, E. M., Ilk, N., Pum, D. & Schuster, B. S-Layers as a basic building block in a molecular construction kit. FEBS J. 274, 323–334 (2007).

    Article  CAS  Google Scholar 

  11. Ringler, P. & Schulz, G. E. Self-assembly of proteins into designed networks. Science 302, 106–109 (2003).

    Article  CAS  Google Scholar 

  12. Dotan, N., Arad, D., Frolow, F. & Freeman, A. Self-assembly of a tetrahedral lectin into predesigned diamondlike protein crystals. Angew. Chem. Int. Ed. 38, 2363–2366 (1999).

    Article  CAS  Google Scholar 

  13. Chau, T. F. et al. Enzyme nanorings. ACS Nano 2, 2519–2525 (2008).

    Article  Google Scholar 

  14. Padilla, J. E., Colovos, C. & Yeates, T. O. Nanohedra: using symmetry to design self assembling protein cages, layers, crystals, and filaments. Proc. Natl Acad. Sci. USA 98, 2217–2221 (2001).

    Article  CAS  Google Scholar 

  15. Schmidt, T. G., Koepke, J., Frank, R. & Skerra, A. Molecular interaction between the Strep-tag affinity peptide and its cognate target, streptavidin. J. Mol. Biol. 255, 753–766 (1996).

    Article  CAS  Google Scholar 

  16. Fairman, R. et al. Design of heterotetrameric coiled coils: evidence for increased stabilization by Glu(–)–Lys(+) ion pair interactions. Biochemistry 35, 2824–2829 (1996).

    Article  CAS  Google Scholar 

  17. Yan, H., Park, S. H., Finkelstein, G., Reif, J. H. & LaBean, T. H. DNA-templated self-assembly of protein arrays and highly conductive nanowires. Science 301, 1882–1884 (2003).

    Article  CAS  Google Scholar 

  18. Dieluweit, S., Pum, D. & Sleytr, U. Formation of a gold superlattice on an S-layer with square lattice symmetry. Supramol. Sci. 5, 15–19 (1998).

    Article  CAS  Google Scholar 

  19. Pleschberger, M. et al. An S-layer heavy chain camel antibody fusion protein for generation of a nanopatterned sensing layer to detect the prostate-specific antigen by surface plasmon resonance technology. Bioconj. Chem. 15, 664–671 (2004).

    Article  CAS  Google Scholar 

  20. Selmi, D. N. et al. DNA-templated protein arrays for single-molecule imaging. Nano Lett. 11, 657–660 (2011).

    Article  CAS  Google Scholar 

  21. Gipson, B., Zeng, X., Zhang, Z. Y. & Stahlberg, H. 2dx—user-friendly image processing for 2D crystals. J. Struct. Biol. 157, 64–72 (2007).

    Article  CAS  Google Scholar 

  22. Crowther, R. A., Henderson, R. & Smith, J. M. MRC image processing programs. J. Struct. Biol. 116, 9–16 (1996).

    Article  CAS  Google Scholar 

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Acknowledgements

The authors thank R. Owen for AFM imaging, E. Valkov, R. Gilbert and members of the LMB, Oxford, for discussions, I. Sinclair for critical reading of the manuscript, and I. Taylor for technical support. The authors are also grateful to Oxford University and Crysalin Ltd for financial support.

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Author notes

  1. Catherine Vénien-Bryan

    Present address: Present address: IMPMC, CNRS-UMR 7590, Université P&M Curie, 4 place Jussieu, 75252 Paris, France,

Authors and Affiliations

  1. Department of Biochemistry, Laboratory of Molecular Biophysics, South Parks Road, Oxford, OX1 3QU, UK

    John C. Sinclair, Karen M. Davies & Martin E. M. Noble

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  1. John C. Sinclair
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Contributions

J.C.S. proposed the original design principle and performed bioinformatics analysis, molecular modelling, cloning of expression constructs, protein production and biophysical characterization, as well as assisting in recording and analysing electron micrographs. K.M.D. recorded the presented electron micrographs and carried out initial image analysis. C.V-B. managed the EM facility and supervised K.M.D. in her contribution. M.E.M.N. worked with J.C.S. to develop the original design, advised on the direction of the research and performed the image analysis presented in Fig. 3. J.C.S. and M.E.M.N. prepared the manuscript with critical comment from all authors.

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Correspondence to John C. Sinclair or Martin E. M. Noble.

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The authors declare no competing financial interests.

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Sinclair, J., Davies, K., Vénien-Bryan, C. et al. Generation of protein lattices by fusing proteins with matching rotational symmetry. Nature Nanotech 6, 558–562 (2011). https://doi.org/10.1038/nnano.2011.122

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