A self-assembled protein β-helix as a self-contained biofunctional motif
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.
Authors
- Erol Hasan (ORCID: https://orcid.org/0009-0003-7610-1887)
- Purnank Aggarwal (ORCID: https://orcid.org/0000-0001-7479-9167)
- Christian D. Lorenz (ORCID: https://orcid.org/0000-0003-1028-4804)
- Javier Garcia-Ruiz (ORCID: https://orcid.org/0000-0002-6718-7231)
- James E. Noble (ORCID: https://orcid.org/0000-0002-7695-536X)
- Camilla Dondi
- Stéphanie Rey (ORCID: https://orcid.org/0000-0002-5476-9208)
- Nilofar Faruqui
- Ibolya E. Kepiro (ORCID: https://orcid.org/0000-0002-8934-3389)
- Andrea Briones
- Maxim G. Ryadnov (ORCID: https://orcid.org/0000-0003-4847-1154)
- Bart W. Hoogenboom (ORCID: https://orcid.org/0000-0002-8882-4324)
- A.T. Fry (ORCID: https://orcid.org/0000-0002-7925-1392)
- Michael Shaw (ORCID: https://orcid.org/0000-0001-6099-3217)
- Alex Hoose
- Antony S. Maxwell
- Poonam Ghai
Institutions
- National Physical Laboratory (GB)
- King's College London (GB)
- London Centre for Nanotechnology (GB)
- King's College School (GB)
- University College London (GB)
- King Abdullah University of Science and Technology (SA)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-05-15
- DOI
- https://doi.org/10.1038/s41467-025-59873-1
- Citations
- 2
- Primary Topic
- Bacteriophages and microbial interactions
- Type
- article
- Field-Weighted Citation Impact
- 3.43
Funders
- King's College London
- National Institutes of Health
- University of Illinois at Urbana-Champaign
- Engineering and Physical Sciences Research Council