Antimicrobial peptides: an atypical double-domain avian defensin, specifically found in eggs, reveals multiple roles in protection of the embryo

08 January 2020 par Isabelle Frapart
Increased biological potency of the double-domain AvBD11 compared to single-domain defensins highlighted by multidisciplinary collaborations based on peptide chemistry, NMR and biology.

Gga-AvBD11, the avian β-defensin 11 of the common chicken Gallus gallus (Gga-AvBD11), is egg-specific, and represents the sole double-sized defensin (9.3 kDa) among the 14 AvBDs reported in the chicken species. The appearance of such a double-domain protein during evolution could be driven either by its increased biological potency compared to a single domain molecule, and/or by the necessity to acquire new functions carried only by the full-length protein. To assess the contribution of the two domains, we chemically synthesized them. We determined the 3D NMR structure each domain, and the structure of the compact full-length Gga-AvBD11, composed of two packed β-defensin domains. There is no reference for such a double-β-defensin in structural databanks. Thus, AvBD11 is the archetype of a new structural family, which we named avian-double-β-defensins (Av-DBD).
Its high sequence conservation among birds suggests its essential roles in the avian egg. In collaboration with several teams (Nouzilly and Tours, France), we showed that Gga-AvBD11 displays antimicrobial activities against Gram+ and Gram- bacterial pathogens, the avian protozoan Eimeria tenella and avian influenza virus (H1N1). It also shows cytotoxic and anti-invasive activities, suggesting that it may be involved in the (re-)modeling of embryonic tissues. Our results point to a critical importance of the cationic N-ter domain in mediating antibacterial, antiparasitic and anti-invasive activities, with the C-ter domain potentiating the two latter activities. Strikingly, antiviral activity in infected chicken cells requires the full-length protein.

The benefit for the avian species of possessing a double-sized defensin is a fascinating question. In order to better understand the structure-activity and phylogenetic relationships of AvBD11s family, we are currently studying other AvBD11 proteins (SAPhyR-11 project grant from the Région Centre Val de Loire).

This work was funded by the MUSE (Grant no. 2014-00094512) and SAPhyR-11 (Grant no. 2017-119983) project grants from the Région Centre-Val de Loire.

Structure, function, and evolution of Gga-AvBD11, the archetype of the structural avian-double- -defensin family
Nicolas Guyot, Hervé Meudal, Sascha Trapp, Sophie Iochmann, Anne Silvestre, Guillaume Jousset, Valérie Labas, Pascale Reverdiau, Karine Loth, Virginie Hervé, Vincent Aucagne, Agnès F. Delmas, Sophie Rehault-Godbert, and Céline Landon