An ancestral host defence peptide within human beta-defensin 3 recapitulates the antibacterial and antiviral activity of the full-length molecule

Nigro, Ersilia; Colavita, Irene; Sarnataro, Daniela; Scudiero, Olga; Zambrano, Gerardo; Granata, Vincenzo; Daniele, Aurora; Carotenuto, Alfonso; Galdiero, Stefania; Folliero, Veronica; Galdiero, Massimiliano; Urbanowicz, Richard; Ball, Jonathan; Salvatore, Francesco; Pessi, Antonello

Abstract

Host defence peptides (HDPs) are critical components of innate immunity. Despite their diversity, they share common features including a structural signature, designated “γ-core motif”. We reasoned that for each HDPs evolved from an ancestral γ-core, the latter should be the evolutionary starting point of the molecule, i.e. it should represent a structural scaffold for the modular construction of the full-length molecule, and possess biological properties. We explored the γ-core of human β-defensin 3 (HBD3) and found that it: (a) is the folding nucleus of HBD3; (b) folds rapidly and is stable in human serum; (c) displays antibacterial activity; (d) binds to CD98, which mediates HBD3 internalization in eukaryotic cells; (e) exerts antiviral activity against human immunodeficiency virus and herpes simplex virus; and (f) is not toxic to human cells. These results demonstrate that the γ-core within HBD3 is the ancestral core of the full-length molecule and is a viable HDP per se,since it is endowed with the most important biological features of HBD3. Notably, the small, stable scaffold of the HBD3 γ-core can be exploited to design disease-specific antimicrobial agents.

Citation

Nigro, E., Colavita, I., Sarnataro, D., Scudiero, O., Zambrano, G., Granata, V., Daniele, A., Carotenuto, A., Galdiero, S., Folliero, V., Galdiero, M., Urbanowicz, R., Ball, J., Salvatore, F., & Pessi, A. (2015). An ancestral host defence peptide within human beta-defensin 3 recapitulates the antibacterial and antiviral activity of the full-length molecule. Scientific Reports, 5, Article 18450. https://doi.org/10.1038/srep18450

• Journal Article Type: Article
• Acceptance Date: Nov 9, 2015
• Online Publication Date: Dec 21, 2015
• Publication Date: Dec 21, 2015
• Deposit Date: Jun 26, 2018
• Publicly Available Date: Jan 29, 2019
• Journal: Scientific Reports
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 5
• Article Number: 18450
• DOI: https://doi.org/10.1038/srep18450
• Public URL: https://nottingham-repository.worktribe.com/output/1114908
• Publisher URL: https://www.nature.com/articles/srep18450