The structure of human beta-defensin-1 - New insights into structural properties of beta-defensins

Defensins are a class of small cationic peptides found in higher organisms that serve as both antimicrobial and cell signaling molecules. The exact me chanism of the antimicrobial activity of defensins is not known, but two mo dels have been postulated, one involving pore formation and the other invol ving nonspecific electrostatic interaction with the bacterial membrane. Her e we report the high resolution structures of human beta -defensin-1 (hBD1) in two crystallographic space groups. The structure of a single molecule i s very similar to that of human beta -defensin-2 (hBD2), confirming the pre sence of an N-terminal alpha -helix. However, while the packing of hBD1 is conserved across both space groups, there is no evidence for any larger qua ternary structure similar to octameric hBD2. Furthermore, the topology of h BD1 dimers that are formed between monomers in the asymmetric unit is disti nct from both hBD2 and other mammalian alpha -defensins. The structures of hBD1 and hBD2 provide a first step toward understanding the structural basi s of antimicrobial and chemotactic properties of human beta -defensins.