Defensin, alpha 6

Human Alpha Defensin 6 belongs to the large group of antimicrobial peptides (AMP), a heterogeneous group of naturally occurring small (< 100 amino acids), cationic amphiphilic, peptides with broad microbicidal activity known as "endogenous antibiotics". Antimicrobial peptides are synthesized by plants, bacteria, insects, invertebrates and vertebrates.

Human antimicrobial peptides play a major role in the innate, non-specific immune defence (see below immunity, innate) within the framework of an epithelial barrier function in the respiratory, urogenital and gastrointestinal tracts as well as in the skin in defending against infectious pathogens. In addition to the cellular epithelial barrier they represent a kind of chemical barrier. Besides their direct antimicrobial functions they also partly act as moderators of inflammatory processes.

The human defensin alpha 6 is a human protein encoded by the DEFA6 gene, which is located on chromosome 8 p23.1 in a gene cluster together with other AMP genes. The members of the defensin family are very similar in their protein sequence and are characterized by a conserved cysteine motif consisting of 6 cysteines.

All alpha-defensins have antimicrobial properties in common. It is assumed that defensins combat pathogens by forming pores in the cell wall, which leads to a loss of membrane stability and ultimately to the death of the pathogen (see below antimicrobial peptides).

Defensin alpha 6 has a high structural similarity to defensin alpha 5 and is also co-expressed with it.

Defensin alpha 6 (HD-6) is exclusively produced by intestinal Paneth cells located at the Bden of Lieberkühn's crypts of the small intestine. One of the main functions of Paneth cells is the secretion of antimicrobial peptides, defensin alpha 5 and defensin alpha 6.

Defensin alpha 6 develops antimicrobial activities against anaerobic intestinal commensals, but not against pathogenic strains.

A reduced expression of defensins alpha 5 and 6 is observed in Crohn's disease, as well as in graft-versus-host disease.

The antibiotic activity of defensin alpha 6 is ensured by reduced peptide formation. This acts independently of the conserved cysteine motif. An oxidoreductase, thioredoxin, formed by the Paneth cells is responsible for this chemical reduction process. (Schroeder BO et al. 2015).

The shortened peptides bind stoichiometrically to the surface of bacteria. There they organize themselves into a finest system of peptide fibrils, so-called nanonets (Chu H et al. 2012), which envelop and inactivate the bacterium (so-called microbial trapping). This form of cell death is also known as NETosis (etosis) and represents a special defence function of the innate immune system (Kaplan MJ 2012).

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