The ß-defensin-fold family of polypeptides

Polypeptides adopting a fold very similar to that of β-defensins are found in diverse organisms, including sea anemones, snakes, platypus and humans. These molecules of ~35–50 amino acid residues possess disparate activities, such as anti-microbial, myonecrotic, analgesic, and ion-channel inhibiting. The family of β-defensin-fold structures generally consists of a short helix or turn followed by a small twisted anti-parallel β-sheet. The six cysteine residues which are paired in a 1–5, 2–4, 3–6 fashion are crucial for determining and maintaining the compact core configuration of the structures. The primary structural similarity between members of the family suggests that the global fold is robust and that the nature of the side-chains determine the functional specificity. The distinct compact fold shared by these polypeptides may be useful in the design of molecules with desired pharmacological activity.