| Primary Identifier | IPR002366 | Type | Domain |
| Short Name | Alpha-defensin_propep |
| description | Defensins are 2-6kDa, cationic, microbicidal peptides active against many Gram-negative and Gram-positive bacteria, fungi, and enveloped viruses [], containing three pairs of intramolecular disulphide bonds []. On the basis of their size and pattern ofdisulphide bonding, mammalian defensins are classified into alpha, beta and theta categories. Alpha-defensins, which have been identified in humans, monkeys and severalrodent species, are particularly abundant in neutrophils, certain macrophage populations and Paneth cells of the small intestine. Every mammalian speciesexplored thus far has beta-defensins. In cows, as many as 13 beta-defensins exist in neutrophils. However, in other species, beta-defensins are more often produced byepithelial cells lining various organs (e.g. the epidermis, bronchial tree and genitourinary tract). Theta-defensins are cyclic and have so far only been identified in primatephagocytes. Defensins are produced constitutively and/or in response to microbial products or proinflammatory cytokines. Some defensins are also called corticostatins (CS) because they inhibit corticotropin-stimulated corticosteroid production. The mechanism(s) by which microorganisms are killed and/or inactivated by defensins is not understood completely. However, it is generally believed that killing is aconsequence of disruption of the microbial membrane. The polar topology of defensins, with spatially separated charged and hydrophobic regions, allows them toinsert themselves into the phospholipid membranes so that their hydrophobic regions are buried within the lipid membrane interior and their charged (mostly cationic)regions interact with anionic phospholipid head groups and water. Subsequently, some defensins can aggregate to form `channel-like' pores; others might bind to and cover the microbial membrane in a `carpet-like' manner. The net outcome is the disruption of membrane integrity and function,which ultimately leads to the lysis of microorganisms. Some defensins are synthesized as propeptides which may be relevant to this process - in neutrophils only the mature peptides have been identified but in Paneth cells, the propeptide is stored in vesicles []and appears to be cleaved by trypsin on activation. |
