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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

Authors

Ersilia Nigro

Irene Colavita

Daniela Sarnataro

Olga Scudiero

Gerardo Zambrano

Vincenzo Granata

Aurora Daniele

Alfonso Carotenuto

Stefania Galdiero

Veronica Folliero

Massimiliano Galdiero

Richard Urbanowicz

Jonathan Ball

Francesco Salvatore

Antonello Pessi



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.

Journal Article Type Article
Publication Date Dec 21, 2015
Journal Scientific Reports
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 5
Article Number 18450
APA6 Citation Nigro, E., Colavita, I., Sarnataro, D., Scudiero, O., Zambrano, G., Granata, V., …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, doi:10.1038/srep18450
DOI https://doi.org/10.1038/srep18450
Publisher URL https://www.nature.com/articles/srep18450

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