title: An ancestral host defence peptide within human β-defensin 3 recapitulates the antibacterial and antiviral activity of the full-length molecule.
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.
authors.affiliation: CEINGE-Biotecnologie Avanzate, Via Gaetano Salvatore 486, 80145 Napoli, Italy.
authors.forename: Ersilia
authors.initials: E
authors.lastname: Nigro
authors.affiliation: CEINGE-Biotecnologie Avanzate, Via Gaetano Salvatore 486, 80145 Napoli, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Colavita
authors.affiliation: CEINGE-Biotecnologie Avanzate, Via Gaetano Salvatore 486, 80145 Napoli, Italy.|Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via Sergio Pansini 5, 80131 Napoli, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Sarnataro
authors.affiliation: CEINGE-Biotecnologie Avanzate, Via Gaetano Salvatore 486, 80145 Napoli, Italy.|Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via Sergio Pansini 5, 80131 Napoli, Italy.
authors.forename: Olga
authors.initials: O
authors.lastname: Scudiero
authors.affiliation: CEINGE-Biotecnologie Avanzate, Via Gaetano Salvatore 486, 80145 Napoli, Italy.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Zambrano
authors.affiliation: CEINGE-Biotecnologie Avanzate, Via Gaetano Salvatore 486, 80145 Napoli, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Granata
authors.affiliation: CEINGE-Biotecnologie Avanzate, Via Gaetano Salvatore 486, 80145 Napoli, Italy.|Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples, Via Vivaldi 43, 81100 Caserta, Italy.
authors.forename: Aurora
authors.initials: A
authors.lastname: Daniele
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Via Domenico Montesano 49, 80131 Napoli, Italy.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Carotenuto
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Via Domenico Montesano 49, 80131 Napoli, Italy.|Institute of Biostructures and Bioimages, CNR, Naples, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Galdiero
authors.affiliation: Department of Experimental Medicine, Second University of Naples, Via Costantinopoli, 16, 80138 Napoli, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Folliero
authors.affiliation: Department of Experimental Medicine, Second University of Naples, Via Costantinopoli, 16, 80138 Napoli, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Galdiero
authors.affiliation: The School of Life Sciences and the Nottingham Digestive Diseases Centre Biomedical Research Unit, The University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, United Kingdom.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Urbanowicz
authors.affiliation: The School of Life Sciences and the Nottingham Digestive Diseases Centre Biomedical Research Unit, The University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, United Kingdom.
authors.forename: Jonathan K
authors.initials: JK
authors.lastname: Ball
authors.affiliation: CEINGE-Biotecnologie Avanzate, Via Gaetano Salvatore 486, 80145 Napoli, Italy.|IRCCS-SDN Foundation, Via Emanuele Gianturco 113, 80142 Napoli, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Salvatore
authors.affiliation: CEINGE-Biotecnologie Avanzate, Via Gaetano Salvatore 486, 80145 Napoli, Italy.
authors.forename: Antonello
authors.initials: A
authors.lastname: Pessi
mesh_terms: D020816:Amino Acid Motifs / Q000235:genetics*; D000890:Anti-Infective Agents / Q000378:metabolism* / Q000627:therapeutic use; D000998:Antiviral Agents / Q000378:metabolism / Q000627:therapeutic use; D027261:Fusion Regulatory Protein-1 / Q000737:chemistry / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017510:Protein Folding; D018139:Simplexvirus / Q000187:drug effects; D023083:beta-Defensins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D000890:Anti-Infective Agents; D000998:Antiviral Agents; C422950:DEFB103A protein, human; D027261:Fusion Regulatory Protein-1; D010455:Peptides; D023083:beta-Defensins