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

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

来源：Scientific Reports, 2015, 5(1): 18450.

DOI：10.1038/srep18450

Host defence peptides (HDPs) are critical components of innate immunity. Despite their diversity, they share common features including a structural signature, designated "gamma-core motif". We reasoned that for each HDPs evolved from an ancestral gamma-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 gamma-core of human beta-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 gamma-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 gamma-core can be exploited to design disease-specific antimicrobial agents.

• 出版日期2015-12-21