Defensin

Defensins are small (15-20 residue) cysteine-rich cationic proteins found in both vertebrates and invertebrates. They are active against bacteria, fungi and enveloped viruses. They consist of 15-20 amino acids including six to eight conserved cysteine residues. Cells of the immune system contain these peptides to assist in killing phagocytized bacteria, for example in neutrophil granulocytes and almost all epithelial cells. Most defensins function by penetrating the microbial's cell membrane by way of electrical attraction, and once embedded, forming a pore in the membrane which allows efflux.

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Varieties

The underlying genes responsible for defensin production are highly polymorphic. Some aspects are conserved, however; the hallmarks of a β-defensin are its small size, high density of cationic charge and six-cysteine-residue motif. Generally they are encoded by two-exon genes, where the first exon encodes for a hydrophobic leader sequence and the second for a peptide containing the cysteine motif.

There are three main (known) forms of mammalian defensins; α-defensins, β-defensins, and θ-defensins.

Function

In immature marsupials, because their immune system is underdeveloped at the time of birth, defensins play a major role in defense against pathogens. They are produced in the milk of the mother as well as by the young marsupial in question. It is also interesting to note that retrocyclin - a theta-defensin^[1] created artificially by `fixing' a human pseudogene - is effective against HIV, though the mechanism by which it does this is unknown.

Also interesting is the effect of defensins on the exotoxin produced by anthrax (bacillus anthracis). Chun Kim et. al showed how anthrax, which produces a metalloprotease Lethal Factor (LF) protein to target MAPKK, is vulnerable to human neutrophil protein-1 (HNP-1). This group showed HNP-1 to behave as a reversible noncompetitive inhibitor of LF.^[2]

Defensins are contained in the sebum secreted by the Sebaceous gland which melts at 30 degrees celsius. Most people in industrialised countries remove the sebum and therefore the defensins every day in the shower.

Pathology

An imbalance of defensins in the skin may contribute to acne.^[3]

A reduction of ileal defensins may predispose to Crohn's disease.^[4][5]

References