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.

• 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