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Short peptides self-assemble to produce catalytic amyloids

Nature Chemistry volume 6, pages 303–309 (2014)Cite this article

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Abstract

Enzymes fold into unique three-dimensional structures, which underlie their remarkable catalytic properties. The requirement to adopt a stable, folded conformation is likely to contribute to their relatively large size (>10,000 Da). However, much shorter peptides can achieve well-defined conformations through the formation of amyloid fibrils. To test whether short amyloid-forming peptides might in fact be capable of enzyme-like catalysis, we designed a series of seven-residue peptides that act as Zn2+-dependent esterases. Zn2+ helps stabilize the fibril formation, while also acting as a cofactor to catalyse acyl ester hydrolysis. These results indicate that prion-like fibrils are able to not only catalyse their own formation, but they can also catalyse chemical reactions. Thus, they might have served as intermediates in the evolution of modern-day enzymes. These results also have implications for the design of self-assembling nanostructured catalysts including ones containing a variety of biological and non-biological metal ions.

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Figure 1: Overview of concept and design.
Figure 2: Functional characterization of the catalysts.
Figure 3: The active species have a β-sheet secondary structure.
Figure 4: Large amyloid fibrils are responsible for catalysis.
Figure 5: Synergistic interactions between peptides.

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Acknowledgements

The authors thank K. L. Mack, G. G. Ariotti, R. P. Doyle, M. M. Maye and R. P. Smith for technical assistance and discussions. This work was in part supported by grant no. GM54616 from the National Institutes of Health (to W.F.D.), grant no. 1332349 from the National Science Foundation (NSF) Emerging Frontiers in Research and Innovation (EFRI) program, and an Oak Ridge Associated Universities Ralph E. Powe Junior Faculty Enhancement award to I.V.K. The authors also acknowledge support from the Materials Research Science and Engineering Center programme of the NSF, grant DMR-1120901.

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Author notes

  1. Caroline M. Rufo, Yurii S. Moroz and Olesia V. Moroz: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Chemistry, Syracuse University, Syracuse, 13244, New York, USA

    Caroline M. Rufo, Yurii S. Moroz, Olesia V. Moroz, Tyler A. Smith & Ivan V. Korendovych

  2. Institute for Neurodegenerative Diseases and Department of Neurology, University of California – San Francisco, San Francisco, 94143, California, USA

    Jan Stöhr

  3. Department of Pharmaceutical Chemistry, University of California – San Francisco, Francisco, 94158, California, USA

    Xiaozhen Hu & William F. DeGrado

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Contributions

C.M.R., Y.S.M., O.V.M., J.S., T.A.S. and X.H. performed the experiments and analysed the data. W.F.D. and I.V.K. conceived and designed the experiments and wrote the manuscript. All authors discussed the results and commented on the manuscript.

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Correspondence to William F. DeGrado or Ivan V. Korendovych.

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Rufo, C., Moroz, Y., Moroz, O. et al. Short peptides self-assemble to produce catalytic amyloids. Nature Chem 6, 303–309 (2014). https://doi.org/10.1038/nchem.1894

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