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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author 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
author_facet 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
author_sort Camilla Dondi
collection DOAJ
description 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.
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spelling doaj-art-84bfa0b53fca4d80829a83fa5ad64e5f2025-08-20T03:53:58ZengNature PortfolioNature Communications2041-17232025-05-0116111810.1038/s41467-025-59873-1A self-assembled protein β-helix as a self-contained biofunctional motifCamilla Dondi0Javier Garcia-Ruiz1Erol Hasan2Stephanie Rey3James E. Noble4Alex Hoose5Andrea Briones6Ibolya E. Kepiro7Nilofar Faruqui8Purnank Aggarwal9Poonam Ghai10Michael Shaw11Antony T. Fry12Antony Maxwell13Bart W. Hoogenboom14Christian D. Lorenz15Maxim G. Ryadnov16National Physical LaboratoryNational Physical LaboratoryNational Physical LaboratoryNational Physical LaboratoryNational Physical LaboratoryNational Physical LaboratoryNational Physical LaboratoryNational Physical LaboratoryNational Physical LaboratoryNational Physical LaboratoryNational Physical LaboratoryNational Physical LaboratoryNational Physical LaboratoryNational Physical LaboratoryLondon Centre for Nanotechnology, University College LondonDepartment of Physics, King’s College LondonNational Physical LaboratoryAbstract 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.https://doi.org/10.1038/s41467-025-59873-1
spellingShingle 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
A self-assembled protein β-helix as a self-contained biofunctional motif
Nature Communications
title A self-assembled protein β-helix as a self-contained biofunctional motif
title_full A self-assembled protein β-helix as a self-contained biofunctional motif
title_fullStr A self-assembled protein β-helix as a self-contained biofunctional motif
title_full_unstemmed A self-assembled protein β-helix as a self-contained biofunctional motif
title_short A self-assembled protein β-helix as a self-contained biofunctional motif
title_sort self assembled protein β helix as a self contained biofunctional motif
url https://doi.org/10.1038/s41467-025-59873-1
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