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

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,...

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Main Authors: Camilla Dondi, Javier Garcia-Ruiz, Erol Hasan, Stephanie Rey, James E. Noble, Alex Hoose, Andrea Briones, Ibolya E. Kepiro, Nilofar Faruqui, Purnank Aggarwal, Poonam Ghai, Michael Shaw, Antony T. Fry, Antony Maxwell, Bart W. Hoogenboom, Christian D. Lorenz, Maxim G. Ryadnov
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-59873-1
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Summary: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.
ISSN:2041-1723