Structure, function, and evolution of Gga -AvBD11, the archetype of the structural avian-double-β-defensin family - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2020

Structure, function, and evolution of Gga -AvBD11, the archetype of the structural avian-double-β-defensin family

Nicolas Guyot
Sascha Trapp
Herve Meudal
Anne Silvestre
Karine Loth
Vincent Aucagne
A.F. Delmas

Résumé

Out of the 14 avian β-defensins identified in the Gallus gallus genome, only 3 are present in the chicken egg, including the egg-specific avian β-defensin 11 (Gga-AvBD11). Given its specific localization and its established antibacterial activity, Gga-AvBD11 appears to play a protective role in embryonic development. Gga-AvBD11 is an atypical double-sized defensin, predicted to possess 2 motifs related to β-defensins and 6 disulfide bridges. The 3-dimensional NMR structure of the purified Gga-AvBD11 is a compact fold composed of 2 packed β-defensin domains. This fold is the archetype of a structural family, dubbed herein as avian-double-β-defensins (Av-DBD). We speculate that AvBD11 emanated from a monodomain gene ancestor and that similar events might have occurred in arthropods, leading to another structural family of less compact DBDs. We show that Gga-AvBD11 displays antimicrobial activities against gram-positive and gram-negative bacterial pathogens, the avian protozoan Eimeria tenella, and avian influenza virus. Gga-AvBD11 also shows cytotoxic and antiinvasive activities, suggesting that it may not only be involved in innate protection of the chicken embryo, but also in the (re)modeling of embryonic tissues. Finally, the contribution of either of the 2 Gga-AvBD11 domains to these biological activities was assessed, using chemically synthesized peptides. Our results point to a critical importance of the cationic N-terminal domain in mediating antibacterial, antiparasitic, and antiinvasive activities, with the C-terminal domain potentiating the 2 latter activities. Strikingly, antiviral activity in infected chicken cells, accompanied by marked cytotoxicity, requires the full-length protein.
Fichier principal
Vignette du fichier
NicolasGuyot_2020_Structure_PNAS.pdf (19.46 Mo) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)

Dates et versions

hal-02522250 , version 1 (24-11-2020)

Identifiants

Citer

Nicolas Guyot, Sascha Trapp, Herve Meudal, Sophie Iochmann, Anne Silvestre, et al.. Structure, function, and evolution of Gga -AvBD11, the archetype of the structural avian-double-β-defensin family. Proceedings of the National Academy of Sciences of the United States of America, 2020, 117 (1), pp.337-345. ⟨10.1073/pnas.1912941117⟩. ⟨hal-02522250⟩
163 Consultations
16 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More