3D NMR structure of hen egg gallin (chicken ovo-defensin) reveals a new variation of the beta-defensin fold [Protein Structure and Folding]

January 17th, 2014 by Herve, V., Meudal, H., Labas, V., Rehault Godbert, S., Gautron, J., Berges, M., Guyot, N., Delmas, A. F., Nys, Y., Landon, C.

Gallin is a 41-residue protein, first identified as a minor component of hen egg white, and found to be antimicrobial against Escherichia coli. Gallin may participate in the protection of the embryo during its development in the egg. Its sequence is related to antimicrobial β-defensin peptides. In the present study, gallin was chemically synthesized 1) to further investigate its antimicrobial spectrum, and 2) to solve its 3D NMR structure, and thus gain insight into structure-function relationships, a prerequisite to understand its mode(s) of action. Antibacterial assays confirmed that gallin was active against Escherichia coli, but no additional antibacterial activity was observed against the other Gram-positive or Gram-negative bacteria tested. The 3D structure of gallin, which is the first ovo-defensin structure to have been solved to date, displays a new five-stranded arrangement. The gallin 3D fold contains the three-stranded antiparallel β-sheet and the disulfide bridge array typical of vertebrate β-defensins. Gallin can therefore be unambiguously classified as a β-defensin. However, an additional short two-stranded β-sheet reveals that gallin, and presumably the other ovo-defensins, form a new structural sub-family of β-defensins. Moreover, gallin and the other ovo-defensins calculated by homology modelling exhibit atypical hydrophobic surface properties, compared with the already known vertebrate β-defensins. These specific structural features of gallin might be related to its restricted activity against E. coli, and/or to other yet unknown functions. This work provides initial understanding of a critical sequence-structure-function relationship for the ovo-defensin family.