Abstract

BackgroundDefensins are antimicrobial peptides of innate immunity functioning by non-specific binding to anionic phospholipids in bacterial membranes. Their cationicity, amphipathicity and ability to oligomerize are considered key factors for their action. Based on structural information on human β-defensin 2, we examine homologous defensins from various mammalian species for conserved functional physico-chemical characteristics.ResultsBased on homology greater than 40%, structural models of 8 homologs of HBD-2 were constructed. A conserved pattern of electrostatics and dynamics was observed across 6 of the examined defensins; models backed by energetics suggest that the defensins in these 6 organisms are characterized by dimerization-linked enhanced functional potentials. In contrast, dimerization is not energetically favoured in the sheep, goat and mouse defensins, suggesting that they function efficiently as monomers.Conclusionβ-defensin 2 from some mammals may work as monomers while those in others, including humans, work as oligomers. This could potentially be used to design human defensins that may be effective at lower concentrations and hence have therapeutic benefits.

Highlights

  • Defensins are antimicrobial peptides of innate immunity functioning by non-specific binding to anionic phospholipids in bacterial membranes

  • The peptides act against bacteria, fungi, and viruses through mechanisms involving membrane disruption or pore formation leading to leakage of cell content and destruction [1]

  • A major family of Antimicrobial peptides (AMPs) found in mammals, plants and insects is that of the defensins – small, cationic peptides containing one or more disulfide bridges

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Summary

Introduction

Defensins are antimicrobial peptides of innate immunity functioning by non-specific binding to anionic phospholipids in bacterial membranes. Their cationicity, amphipathicity and ability to oligomerize are considered key factors for their action. Based on structural information on human β-defensin 2, we examine homologous defensins from various mammalian species for conserved functional physico-chemical characteristics. Antimicrobial peptides (AMPs) are important components of the innate immunity of a wide range of organisms and present the first line of defence against invading microorganisms. The human β-defensins have potent antimicrobial activity and attract T-lymphocytes and immature dendritic cells as part of an inflammatory response, thereby playing a key role in adaptive immunity [3]

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