Design, structural and functional characterization of human beta defensin analogs

Abstract

Defensins comprises a large family of antimicrobial peptides with fewer than 100 amino acids and with either three or four disulfide bonds. Most of them are cationic and seen in all humans, animals, plants and insects. Among them Human Beta Defensin - 3 (HBD-3) is known to exhibit many interesting behaviors like high positive charge (+11), very broad spectrum of activity in a comparatively low salt sensitive manner, low lytic activity on the human erythrocytes and no cytotoxic effect against human cells. In order to explore the importance of the three dimensional structure of HBD-3 in its activity and selectivity, we have mutated all its six cysteine residues to other amino acids to express a linear analogue (named as Def-A) in E. coli and characterize the mutant¿s activity, binding, structure and dynamics. Our experiment provides the data about what will be the structure and dynamics of HBD-3 when all its cysteine residues are mutated and subjected to different model membranes. This study also tells about the importance of the defensin fold for the selectivity, potency and behavior of this peptide through the structural basis.