biostudies-literatureBera SEuropean Research Council503-509https://www.ebi.ac.uk/biostudies/studies/S-EPMC7616940biostudies-literatureUnknown18(5)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.Nature materialsRigid helical-like assemblies from a self-aggregating tripeptide.PMC7616940694426Bera SMondal SXue BShimon LJWCao YGazit EfalseRigid 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.2019-01-01T00:00:00Z2019 May2026-04-08T19:49:11.841Z2025-04-04T12:25:33.765ZS-EPMC76169403098845010.1038/s41563-019-0343-2