The human beta-defensin-3, an antibacterial peptide with multiple biological functions.

A group of interesting molecules called defensins exhibit multiple functions but have been primarily recognized to possess a broad spectrum of antimicrobial activities. Studies have reported two different types of defensins (alpha and beta) from human and animals, a cyclic theta defensin from rhesus, and several defensin-like peptides from plants. There is no amino acid sequence homology between these peptides, but they all contain three Cys-Cys disulfide linkages while the connectivities are different. Human beta-defensin-3 (HbetaD-3) is the most recently discovered member of the host-defense peptide family that has attracted much attention. This molecule is expressed either constitutively or induced upon a challenge, and a growing evidence indicates the involvement of such molecules in adaptive immunity as well. It has been shown to exhibit antibacterial activities towards Gram-negative and Gram-positive bacteria as well as an ability to act as a chemo-attractant. Analysis of NMR structural data suggested a symmetrical dimeric form of this peptide in solution, which consists of three beta strands and a short helix in the N-terminal region. While the disulfide linkages are known to provide the structural stability and stability against proteases, the biological relevance of this dimeric form was contradicted by another biological study. Since there is considerable current interest in developing HbetaD-3 for possible pharmaceutical applications, studies to further our understanding on the determinants of antibacterial activities and immunomodulatory function of HbetaD-3 are considered to be highly significant. The knowledge of its biosynthetic regulation will also help in understanding the role of HbetaD-3 in immunity. This article presents an overview of the expression and regulation of HbetaD-3 in humans, and the structure-function correlations among HbetaD-3 and its modified peptides are discussed emphasizing the functional importance. The future scope for studies on HbetaD-3 and design of short potent antimicrobial peptides, based on the native HbetaD-3 molecule, that do not interfere in the immunomodulatory function is also outlined.