Defensins are defined as small, 3-4 kDa antimicrobial peptides that contain six disulfide-paired cysteines. These disulfide bonds are unusual on such a small peptide (containing on average about 35 amino acids). While these disulfide bonds prevent any gross conformational changes, they do however provide the necessary stability for the defensins to function properly. To the left, Insect Defensin-A is depicted. This defensin provides a clear and simple example for the structure of defensins. Each of its six paired cystines are shown, as well as its three disulfide bonds.
Defensin peptides also have a triple stranded b-sheet structure with a hydrophobic b-hairpin which protrudes nearly orthogonally. To the left, Insect Defensin is again used to provide a simple illustration of this. The b-hairpin is shown in red.
Also, as mentioned before, the peptides are cationic. This is a result of arginine as the predominant cationic residue. The cysteine residues are usually spread out evenly throughout the peptide chain, except that there is usually a single pair that is located next to each other. Typically, it is the C5 and C6 residues which are located near the carboxyl terminus; however, in humans there is another pair, C1 and C2, which are near the N terminus and are separated by a single residue. The sequence for human HNP-1 is pictured below.
However, while insect defensin is a provides a clear,
simple example of defensins, Human HNP-3 Defensin, shown to the left with disulfide bonds highlighted, is slightly more complex. Since it and all human defensins occur in dimers, it contains a total of six disulfide bonds. Additionally, as with the disulfide bond system, the b-sheet structures within human defensins are also somewhat more complex. The two molecules composing this asymmetric unit are related to one another by a local twofold rotation axis. The three strandedb-sheet of the monomers are exteneded across this interface to form a six stranded sheet in the dimer. Below, the three b-sheet consisting each monomer are depicted, with theb-hairpins highlighted in red. Also shown below are the hydrogen bonds linking the b-sheets with the disulfide bonds shown as lightning bolts.
This dimeric association is further stabalized by hydrophobic interactions, especially between Cys5, Cys20, Tyr22, and Phe28 from each of the monomers. Below is an image of the placement of these residues in the interface between the two monomers.
