3D structures of avian defensins

PosterNational audienceVertebrate defensins play a major role in both innate and adaptive immunity. They display wide range of microbicidal or microbistatic activities against Gram-negative and Gram positive bacteria, fungi and viruses. Three subclasses (a, 13. and 9) have been defined depending on the disulfide pairing involving the six conserved cysteines. We determined the three 3D-structures of avian defensins currently available: - We first resolved the solution structure of the king penguin AvBD103b defensin in 2004 (PDB code 1ut3). This first report on the 3D structure of avian defensin is structurally very close to mammal beta-defensins, but display different surface properties, certainly linked to a different mode of action at the level of the bacterial membranes. - We recently published the chicken AvBD2 solution structure (PDB code 2gl5) as well as its mutant AvBD2-K31A (substitution of a lysine residue for an alanine residue, PDB code 2gl6), which allows us to draw the first insights into structure activity relationships. - Finally, we determined the first 3D-structure of an ovo-defensin, gallin from chicken egg (PDB code 21gv), which unambiguously allows classifying it in 13-defensin's sub-family, even with some special structural features. Moreover, this first ovo-defensin structure can be used as a template to modelize other ovo-defensins from other birds. The overall folds of these three avian defensins include the typical twisted three-stranded antiparallel 13-sheet of 13-defensins, with the disulfide bridges pairing C1 -C5, C3-C6 and C2- C4. When the 3D-structures of king penguin AvBD1 03b, chicken AvBD2 and chicken egg gallin are compared, the three-stranded 13-sheet can be easily superimposed. However they differ in their N-terminal part. While AvBD1 03b has a high propensity to form an alpha-helix in aqueous solution, as it has been observed for related mammal 13defensins, gallin contains an additional parallel two-stranded beta-sheet, that had never been observed before for other defensins regardless their origin or subclasses. Chicken AvBD2 is shorter, lacking the N terminal residues and consequently has no possibility to form an additional N-terminal structural element