Dondi, C; Garcia-Ruiz, J; Hasan, E; Rey, S; Noble, J E; Hoose, A; Briones, A; Kepiro, I E; Faruqui, N; Aggarwal, P; Ghai, P; Shaw, M; Fry, A T; Maxwell, A; Hoogenboom, B W; Lorenz, C D; Ryadnov, M G (2025) A self-assembled protein β-helix as a self-contained biofunctional motif. Nature Communications, 16. 4535 ISSN 2041-1723

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Abstract

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.

Item Type:	Article
Subjects:	Biotechnology > Biopharmaceutical Manufacturing and Characterisation
Divisions:	Chemical & Biological Sciences
Identification number/DOI:	10.1038/s41467-025-59873-1
Last Modified:	12 Mar 2026 10:57
URI:	https://eprintspublications.npl.co.uk/id/eprint/10308