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Rigid helical-like assemblies from a self-aggregating tripeptide


The structural versatility, biocompatibility and dynamic range of the mechanical properties of protein materials have been explored in functional biomaterials for a wide array of biotechnology applications. Typically, such materials are made from self-assembled peptides with a predominant β-sheet structure, a common structural motif in silk and amyloid fibrils. However, collagen, the most abundant protein in mammals, is based on a helical arrangement. Here we show that Pro-Phe-Phe, the most aggregation-prone tripeptide of natural amino acids, assembles into a helical-like sheet that is stabilized by the dry hydrophobic interfaces of Phe residues. This architecture resembles that of the functional PSMα3 amyloid, highlighting the role of dry helical interfaces as a core structural motif in amyloids. Proline replacement by hydroxyproline, a major constituent of collagen, generates minimal helical-like assemblies with enhanced mechanical rigidity. These results establish a framework for designing functional biomaterials based on ultrashort helical protein elements.

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Fig. 1: Amyloid-like fibrillar assembly of Pro-Phe-Phe.
Fig. 2: Single-crystal structure of Pro-Phe-Phe in P21 space group.
Fig. 3: Supramolecular helical architecture.
Fig. 4: Strength modulation of helical-like architecture via side-chain modification.

Data availability

Crystal data for Pro-Phe-Phe, Hyp-Phe-Phe, Ala-Phe-Phe and Ala-Phe-Ala are available from the Cambridge Crystallographic Data Centre (CCDC) under reference nos. 1565666, 1823367, 1862583 and 1834550, respectively ( The remaining data supporting the findings of this study are within the Article and its Supplementary Information files and are available from the corresponding author upon reasonable request.


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S.B. thanks Tel Aviv University for a post-doctoral fellowship. S.M. thanks the PBC Program for a scholarship. This project received funding from ERC under the European Union Horizon 2020 Research and innovation programme (grant agreement no. BISON-694426 to E.G.). Y.C. acknowledges support from the National Natural Science Foundation of China (grants nos. 11804148 and 11804147). The authors thank D. Levy (Tel Aviv University) for support with powder X-ray diffraction and data analysis. The authors thank S. Rencus-Lazar for help with scientific and language editing.

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Authors and Affiliations



S.B., S.M. and E.G. designed the experiments. S.B. performed the experiments and crystallized the peptides. B.X. and Y.C. measured the Young’s modulus and analysed the data. L.J.W.S. collected the single-crystal diffraction data and solved the crystal structures. S.B., S.M. and E.G. wrote the paper. All authors commented on the manuscript.

Corresponding author

Correspondence to Ehud Gazit.

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The authors declare no competing interests.

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Supplementary information

Supplementary Information

Supplementary Figs. 1–20, Supplementary Notes 1–2, Supplementary Tables 1–4, Supplementary refs. 1–17

Reporting Summary

Supplementary Data 1

Crystallographic information file for single crystal structure of the tripeptide Pro-Phe-Phe.

Supplementary Data 2

Crystallographic information file for single crystal structure of the tripeptide Hyp-Phe-Phe.

Supplementary Data 3

Crystallographic information file for single crystal structure of the tripeptide Ala-Phe-Ala.

Supplementary Data 4

Crystallographic information file for single crystal structure of the tripeptide Ala-Phe-Phe.

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Bera, S., Mondal, S., Xue, B. et al. Rigid helical-like assemblies from a self-aggregating tripeptide. Nat. Mater. 18, 503–509 (2019).

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