A self-assembled protein β-helix as a self-contained biofunctional motif

2025-05-15

Nature constructs matter by employing protein folding motifs, many of which have been synthetically reconstituted to exploit function. A less understood motif whose structure-function relationships remain unexploited is formed by parallel β-strands arranged in a helical repetitive pattern, termed a β-helix. Herein we reconstitute a protein β-helix by design and endow it with biological function. Unlike β-helical proteins, which are contiguous covalent structures, this β-helix self-assembles from an elementary sequence of 18 amino acids. Using a combination of experimental and computational methods, we demonstrate that the resulting assemblies are discrete cylindrical structures exhibiting conserved dimensions at the nanoscale. We provide evidence for the structures to form a carpet-like three-dimensional scaffold promoting and inhibiting the growth of human and bacterial cells, respectively, while being able to mediate intracellular gene delivery. The study introduces a self-assembled β-helix as a self-contained bio- and multi-functional motif for exploring and exploiting mechanistic biology.

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DOI https://doi.org/10.1038/s41467-025-59873-1