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

Abstract

Defensins are a class of small cationic peptides found in higher organisms that serve as both antimicrobial and cell signaling molecules. The exact mechanism of the antimicrobial activity of defensins is not known, but two models have been postulated, one involving pore formation and the other involving nonspecific electrostatic interaction with the bacterial membrane. Here we report the high resolution structures of human beta-defensin-1 (hBD1) in two crystallographic space groups. The structure of a single molecule is very similar to that of human beta-defensin-2 (hBD2), confirming the presence 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 quaternary structure similar to octameric hBD2. Furthermore, the topology of hBD1 dimers that are formed between monomers in the asymmetric unit is distinct from both hBD2 and other mammalian alpha-defensins. The structures of hBD1 and hBD2 provide a first step toward understanding the structural basis of antimicrobial and chemotactic properties of human beta-defensins.