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Catalytic diversity in self-propagating peptide assemblies

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.

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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).

    CAS  Article  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).

    CAS  Article  Google Scholar 

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

    CAS  Article  Google Scholar 

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

    CAS  Article  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).

    CAS  Article  Google Scholar 

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

    CAS  Article  Google Scholar 

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

    CAS  Article  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).

    CAS  Article  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).

    CAS  Article  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).

    CAS  Article  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).

    CAS  Article  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).

    CAS  Article  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).

    CAS  Article  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).

    CAS  Article  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).

    CAS  Article  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).

    CAS  Article  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).

    CAS  Article  Google Scholar 

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

    CAS  Article  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).

    CAS  Article  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).

    CAS  Article  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).

    CAS  Article  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).

    CAS  Article  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).

    CAS  Article  Google Scholar 

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

    CAS  Article  Google Scholar 

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

    CAS  Article  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).

    CAS  Article  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).

    CAS  Article  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).

    CAS  Article  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).

    CAS  Article  Google Scholar 

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

    CAS  Article  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).

    CAS  Article  Google Scholar 

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

    CAS  Article  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).

    CAS  Article  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).

    CAS  Article  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).

    CAS  Article  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).

    CAS  Article  Google Scholar 

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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.

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Correspondence to David G. Lynn.

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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

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