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

Abstract

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.

In Vitro and In Vivo Anticancer Activity of Human β-Defensin-3 and Its Mouse Homolog

“…This may have occurred because of differences in the concentration of hBD3 and Defb14 used, although the concentration of 20 μg/ml defensin used in our study was not excessively higher than that at which antimicrobial activity was observed (10). Additionally, different pathways may function, if the tumors themselves overexpress defensin (15,27).…”

“…In contrast to other defensin isoforms, the prominent features of hBD3 antimicrobial activity are its salt-independency and its broad antimicrobial spectrum (7,10,11).…”

Detection of Antimicrobial Effect of Extracellular Protein Produced by Psychrophilic Actinomycetes Isolated From Manali Ice Point

“…These peptides include two or more positively charged residues provided by arginine, lysine or, in acidic environments, histidine, and a large proportion (generally>50%) of hydrophobic residues. The secondary structures of these molecules follow 4 themes, including i) α-helical ii) β-stranded due to the presence of 2 or more disulfide bonds, iii) beta-hairpin or loop due to the presenc of a single disulfide bond and/ or cyclization of the peptide chain, and iv) extended 9 . Many of these peptides are unstructured in free solution, and fold into their final configuration upon partitioning into biological membranes.…”

Human Beta Defensins 1, 2 and 3 Produced by Amniochorion Membranes Is Similar in Term and Preterm Delivery

“…The antimicrobial activity is explained by the ability to the HBD2, for example, to inhibit the LPS action and block the inflammation by the LPS-induced TNF-α production [25]. The similar way HBD3 is able to neutralize LPS 26], besides an in vitro study with S. aureus showed that its action is in the plasma membrane since it has the capability to cause morphological changes in the peripheral cell wall [21]. Moreover, HBD3 has a broad spectrum of antimicrobial activity against several pathogenic bacteria at low concentrations and independent of the sodium concentration [21].…”