Beta/alpha defensin (IPR006080)
Short name: Defensin_beta/alpha
Overlapping homologous superfamilies
- Beta/alpha defensin (IPR006080)
- Alpha-defensin (IPR006081)
Defensins are 2-6 kDa, cationic, microbicidal peptides active against many Gram-negative and Gram-positive bacteria, fungi, and enveloped viruses [PMID: 8528769], containing three pairs of intramolecular disulphide bonds. On the basis of their size and pattern of disulphide bonding, mammalian defensins are classified into alpha, beta and theta categories. Alpha-defensins, which have been identified in humans, monkeys and several rodent species, are particularly abundant in neutrophils, certain macrophage populations and Paneth cells of the small intestine. Every mammalian species explored 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 by epithelial 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 primate phagocytes.
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 a consequence of disruption of the microbial membrane. The polar topology of defensins, with spatially separated charged and hydrophobic regions, allows them to insert 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.
Neutrophil alpha-defensin has antimicrobial activity against Gram-negative bacteria, and to a lesser extent also against Gram-positive bacteria and fungi. It also protects blood cells against infection with HIV-1 (in vitro) and inhibits corticotropin (ACTH)-stimulated corticosterone production [PMID: 15616305, PMID: 15620707].
- SM00048 (DEFSN)