Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Catalytic diversity in self-propagating peptide assemblies

Nature Chemistry volume 9, pages 805–809 (2017)Cite this article

Subjects

Abstract

The protein-only infectious agents known as prions exist within cellular matrices as populations of assembled polypeptide phases ranging from particles to amyloid fibres. These phases appear to undergo Darwinian-like selection and propagation, yet remarkably little is known about their accessible chemical and biological functions. Here we construct simple peptides that assemble into well-defined amyloid phases and define paracrystalline surfaces able to catalyse specific enantioselective chemical reactions. Structural adjustments of individual amino acid residues predictably control both the assembled crystalline order and their accessible catalytic repertoire. Notably, the density and proximity of the extended arrays of enantioselective catalytic sites achieve template-directed polymerization of new polymers. These diverse amyloid templates can now be extended as dynamic self-propagating templates for the construction of even more complex functional materials.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Morphology and structural models of the LVFFA peptide nanotubes.
Figure 2: Oligomerization with K1 nanotubes.
Figure 3: Retro-aldol catalysis by peptide cross-β assemblies.
Figure 4: Kinetic analysis of retro-aldol cleavage.

References

  1. Sipe, J. D. & Cohen, A. S. Review: history of the amyloid fibril. J. Struct. Biol. 130, 88–98 (2000).

    Article  CAS  Google Scholar 

  2. Astbury, W. T., Dickinson, S. & Bailey, K. The X-ray interpretation of denaturation and the structure of the seed globulins. Biochem. J. 29, 2351–2360 (1935).

    Article  CAS  Google Scholar 

  3. Parker, K. D. & Rudall, K. M. Structure of the silk of Chrysopa egg-stalks. Nature 179, 905–906 (1957).

    Article  CAS  Google Scholar 

  4. Eanes, E. D. & Glenner, G. G. X-ray diffraction studies on amyloid filaments. J. Histochem. Cytochem. 16, 673–677 (1968).

    Article  CAS  Google Scholar 

  5. Geddes, A. J. P., Parker, K. D., Atkins, E. D. T. & Beighton, E. “Cross-β” conformation in proteins. J. Mol. Biol. 32, 343–358 (1968).

    Article  CAS  Google Scholar 

  6. Mehta, A. K. et al. Facial symmetry in protein self-assembly. J. Am. Chem. Soc. 130, 9829–9835 (2008).

    Article  CAS  Google Scholar 

  7. Aguzzi, A., Baumann, F. & Bremer, J. The prion's elusive reason for being. Annu. Rev. Neurosci. 31, 439–477 (2008).

    Article  CAS  Google Scholar 

  8. Tkachenko, A. V. & Maslov, S. Spontaneous emergence of autocatalytic information-coding polymers. J. Chem. Phys. 143, 045102 (2015).

    Article  Google Scholar 

  9. Chernoff, Y. O. Amyloidogenic domains, prions and structural inheritance: rudiments of early life or recent acquisition? Curr. Opin. Chem. Biol. 8, 665–671 (2004).

    Article  CAS  Google Scholar 

  10. Sanders, D. W., Kaufman, S. K., Holmes, B. B. & Diamond, M. I. Prions and protein assemblies that convey biological information in health and disease. Neuron 89, 433–448 (2016).

    Article  CAS  Google Scholar 

  11. Williams, A. D. et al. Mapping Aβ amyloid fibril secondary structure using scanning proline mutagenesis. J. Mol. Biol. 335, 833–842 (2004).

    Article  CAS  Google Scholar 

  12. Williams, A. D., Shivaprasad, S. & Wetzel, R. Alanine scanning mutagenesis of Aβ(1–40) amyloid fibril stability. J. Mol. Biol. 357, 1283–1294 (2006).

    Article  CAS  Google Scholar 

  13. Childers, W. S., Mehta, A. K., Lu, K. & Lynn, D. G. Templating molecular arrays in amyloid's cross-β grooves. J. Am. Chem. Soc. 131, 10165–10172 (2009).

    Article  CAS  Google Scholar 

  14. Childers, W. S., Mehta, A. K., Ni, R., Taylor, J. V. & Lynn, D. G. Peptides organized as bilayer membranes. Angew. Chem. Int. Ed. 49, 4104–4107 (2010).

    Article  CAS  Google Scholar 

  15. Kalaiselvi, D., Mohan Kumar, R. & Jayavel, R. Crystal growth, thermal and optical studies of semiorganic nonlinear optical material: L-lysine hydrochloride dihydrate. Mater. Res. Bull. 43, 1829–1835 (2008).

    Article  CAS  Google Scholar 

  16. Lassila, J. K., Baker, D. & Herschlag, D. Origins of catalysis by computationally designed retroaldolase enzymes. Proc. Natl Acad. Sci. USA 107, 4937–4942 (2010).

    Article  CAS  Google Scholar 

  17. List, B., Barbas, C. F. & Lerner, R. A. Aldol sensors for the rapid generation of tunable fluorescence by antibody catalysis. Proc. Natl Acad. Sci. USA 95, 15351–15355 (1998).

    Article  CAS  Google Scholar 

  18. Balbach, J. J. et al. Amyloid fibril formation by Aβ16-22, a seven-residue fragment of the Alzheimer's β-amyloid peptide, and structural characterization by solid state NMR. Biochemistry 39, 13748–13759 (2000).

    Article  CAS  Google Scholar 

  19. Liang, C. et al. Kinetic intermediates in amyloid assembly. J. Am. Chem. Soc. 136, 15146–15149 (2014).

    Article  CAS  Google Scholar 

  20. Childers, W. S., Mehta, A. K., Bui, T. Q., Liang, Y. & Lynn, D. G. in Molecular Self-Assembly: Advances and Applications (ed. Li, A.) Ch. 1, 1–36 (Pan Stanford Publishing, 2012).

    Book  Google Scholar 

  21. Liang, Y. et al. Cross-strand pairing and amyloid assembly. Biochemistry 47, 10018–10026 (2008).

    Article  CAS  Google Scholar 

  22. Michaelis, L. & Menten, M. L. Die kinetik der invertinwirkung. Biochem. Z. 49, 333–369 (1913).

    CAS  Google Scholar 

  23. Chen, W. W., Niepel, M. & Sorger, P. K. Classic and contemporary approaches to modeling biochemical reactions. Genes Dev. 24, 1861–1875 (2010).

    Article  CAS  Google Scholar 

  24. Johnsson, K., Allemann, R. K., Widmer, H. & Benner, S. A. Synthesis, structure and activity of artificial, rationally designed catalytic polypeptides. Nature 365, 530–532 (1993).

    Article  CAS  Google Scholar 

  25. Reymond, J.-L. & Chen, Y. Catalytic, enantioselective aldol reaction using antibodies against a quaternary ammonium ion with a primary amine cofactor. Tetrahedron Lett. 36, 2575–2578 (1995).

    Article  CAS  Google Scholar 

  26. Wagner, J., Lerner, R. A. & Barbas, C. F. Efficient aldolase catalytic antibodies that use the enamine mechanism of natural enzymes. Science 270, 1797–1800 (1995).

    Article  CAS  Google Scholar 

  27. Hoffmann, T. et al. Aldolase antibodies of remarkable scope. J. Am. Chem. Soc. 120, 2768–2779 (1998).

    Article  CAS  Google Scholar 

  28. Tanaka, F. Development of protein, peptide, and small molecule catalysts using catalysis-based selection strategies. Chem. Rec. 5, 276–285 (2005).

    Article  CAS  Google Scholar 

  29. Müller, M. M., Windsor, M. A., Pomerantz, W. C., Gellman, S. H. & Hilvert, D. A rationally designed aldolase foldamer. Angew. Chem. Int. Ed. 48, 922–925 (2009).

  30. Ruscio, J. Z., Kohn, J. E., Ball, K. A. & Head-Gordon, T. The influence of protein dynamics on the success of computational enzyme design. J. Am. Chem. Soc. 131, 14111–14115 (2009).

    Article  CAS  Google Scholar 

  31. Liang, Y. et al. Light harvesting antenna on an amyloid scaffold. Chem. Commun. 2008, 6522–6524 (2008).

    Article  Google Scholar 

  32. Liu, P. et al. Nucleobase-directed amyloid nanotube assembly. J. Am. Chem. Soc. 130, 16867–16869 (2008).

    Article  CAS  Google Scholar 

  33. Dong, J., Shokes, J. E., Scott, R. A. & Lynn, D. G. Modulating amyloid self-assembly and fibril morphology with Zn(II). J. Am. Chem. Soc. 128, 3540–3542 (2006).

    Article  CAS  Google Scholar 

  34. Dong, J. et al. Engineering metal ion coordination to regulate amyloid fibril assembly and toxicity. Proc. Natl Acad. Sci. USA 104, 13313–13318 (2007).

    Article  CAS  Google Scholar 

  35. Goodwin, J. T., Mehta, A. K. & Lynn, D. G. Digital and analog chemical evolution. Acc. Chem. Res. 45, 2189–2199 (2012).

    Article  CAS  Google Scholar 

  36. Goodwin, J. T. et al. Alternative Chemistries of Life: Empirical Approaches (NASA, NSF, 2014).

    Google Scholar 

  37. Rufo, C. M. et al. Short peptides self-assemble to produce catalytic amyloids. Nat. Chem. 6, 303–309 (2014).

    Article  CAS  Google Scholar 

  38. Korendovych, I. V. & DeGrado, W. F. Catalytic efficiency of designed catalytic proteins. Curr. Opin. Struct. Biol. 27, 113–121 (2014).

    Article  CAS  Google Scholar 

  39. Chen, C. et al. Design of multi-phase dynamic chemical networks. Nat. Chem. http://dx.doi.org/10.1038/nchem.2737 (2017).

  40. Turner, J. M., Bui, T., Lerner, R. A., Barbas, C. F. III & List, B. An efficient benchtop system for multigram-scale kinetic resolutions using aldolase antibodies. Chem. Eur. J. 6, 2772–2774 (2000).

    Article  CAS  Google Scholar 

  41. Anthony, N. R., Mehta, A. K., Lynn, D. G. & Berland, K. M. Mapping amyloid-β(16-22) nucleation pathways using fluorescence lifetime imaging microscopy. Soft Matter 10, 4162–4172 (2014).

    Article  CAS  Google Scholar 

  42. Mohamadi, F. et al. Macromodel — an integrated software system for modeling organic and bioorganic molecules using molecular mechanics. J. Comput. Chem. 11, 440–467, (1990).

    Article  CAS  Google Scholar 

  43. Bowers, K. J . et al. Scalable algorithms for molecular dynamics simulations on commodity clusters. In SC ‘06 Proc. 2006 ACM/IEEE Conf. on Supercomputing 84 (2006).

    Google Scholar 

  44. Berendsen, H., Postma, J., Van Gunsteren, W. & Hermans, J. Interaction models for water in relation to protein hydration. Intermol. Forces 11, 331–342 (1981).

    Article  Google Scholar 

  45. Kaminski, G. A., Friesner, R. A., Tirado-Rives, J. & Jorgensen, W. L. Evaluation and reparametrization of the OPLS-AA force field for proteins via comparison with accurate quantum chemical calculations on peptides. J. Phys. Chem. B. 105, 6474–6487 (2001).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We are grateful to J. Taylor and H. Yi in the Emory Robert P. Apkarian Microscopy Core for TEM advice and training. This work was supported initially by the McDonnell Foundation, transiently by NSF and the NASA Astrobiology Program, under the NSF Center for Chemical Evolution, CHE-1004570, and then predominantly funded by Emory University, The Division of Chemical Sciences, Geosciences, and Biosciences, Office of Basic Energy Sciences of the US Department of Energy through Grant DE-ER15377 for peptide synthesis and assembly characterization, and NSF CHE-1507932 for personnel, supplies, equipment, and structural characterization support.

Author information

Authors and Affiliations

  1. Departments of Chemistry and Biology, Emory University, Atlanta, 30322, Georgia, USA

    Tolulope O. Omosun, W. Seth Childers, Dibyendu Das, Anil K. Mehta, Ting Pan & David G. Lynn

  2. School of Chemical Engineering, Georgia Institute of Technology, Atlanta, 30332, Georgia, USA

    Ming-Chien Hsieh & Martha A. Grover

  3. Department of Physics, Emory University, Atlanta, 30322, Georgia, USA

    Neil R. Anthony & Keith M. Berland

Authors
  1. Tolulope O. Omosun
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ming-Chien Hsieh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. W. Seth Childers
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dibyendu Das
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Anil K. Mehta
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Neil R. Anthony
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ting Pan
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Martha A. Grover
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Keith M. Berland
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. David G. Lynn
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed significantly to the design of experiments, analysing the data and drafting of the manuscript.

Corresponding author

Correspondence to David G. Lynn.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary information

Supplementary information (PDF 1481 kb)

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Omosun, T., Hsieh, MC., Childers, W. et al. Catalytic diversity in self-propagating peptide assemblies. Nature Chem 9, 805–809 (2017). https://doi.org/10.1038/nchem.2738

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nchem.2738

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing