Résumé
Protegrins (PG-1 to 5) are a family of five short antibacterial peptides (16–18 residues) characterized by their high content in cysteine and arginine residues which adopt a β-sheet structure stabilized by two disulfide bridges [1]. Protegrins are initially produced as an inactive precursor protein of 149 residues which consists of a peptide signal (1–28), a pro-sequence (ProS) of 101 residues (29–130) and the protegrin sequence (131–147/148) [2]. The active protegrin is released by cleavage of the V130R131 amide bond by an elastase-like enzyme [3]. Electrostatic interactions between PG-3 and its pro-sequence are supposed to suppress the antibacterial activity of PG-3. Interestingly, very similar pro-sequences are encountered in more than 15 antibacterial peptides of unrelated structures and are referred to as a cathelicidin motif [4,5]. The three-dimensional structure of this wide spread motif which contains two conserved disulfide bonds (85–96 and 107–124 in ProS) is not yet known. Despite a low sequence similarity (20%) with the chicken cystatin, a similar fold was hypothesized for the cathelicidin motif. This investigation was designed to determine the three-dimensional structure of ProS (the cathelicidin motif) as well as its interactions with PG supposed to be responsible for the loss of the antibacterial activity of PG-3. Here, we report the over-expression of the ProS and preliminary results of its structural study.