Alpha defensin
Gene Aliases Peptide Sequence
DEFA1 HNP1 human neutrophil peptide 1 ACYCRIPACIAGERRYGTCIYQGRLWAFCC
HNP2 human neutrophil peptide 2 CYCRIPACIAGERRYGTCIYQGRLWAFCC
DEFA3 HNP3 human neutrophil peptide 3 DCYCRIPACIAGERRYGTCIYQGRLWAFCC
DEFA4 HNP4 human neutrophil peptide 4 VCSCRLVFCRRTELRVGNCLIGGVSFTYCCTRV
DEFA5 HD5 human defensin 5 ATCYCRHGRCATRESLSGVCEISGRLYRLCCR
DEFA6 HD6 human defensin 6 AFTCHCRRSCYSTEYSYGTCTVMGINHRFCCL
Structure
HNP-1 , HNP-2 and HNP-3 are encoded by two genes DEFA1 and DEFA3 localized at chromosome 8 , location 8p23.1 . DEFA1 and DEFA3 encode identical peptides except the conversion of the first amino acid from alanine in HNP-1 to aspartic acid in HNP-3 ; HNP-2 is an N-terminally truncated iso-form lacking the first amino acid . Human neutrophil peptides are found in human atherosclerotic arteries , inhibit LDL metabolism and fibrinolysis and promote Lp ( a ) binding . [ 3 ] Like other alpha-defensins , cryptdins are small , 32-36 amino acid long cationic peptides . They possess 6 conserved cysteines that form a tridisulfide array with an arrangement of cysteine pairings that typify alpha-defensins . Cryptdins also display a secondary and tertiary structure that is dominated by a three-stranded beta-sheet . The topology that arises from this structure is an amphipathic globular form in which the termini are paired opposite a pole including a cluster of cationic residues . [ 4 ] Sequences of major human α-defensins : [ 5 ]
Alpha defensins are a family of mammalian defensin peptides. Defensins are 2-6 kDa, cationic, microbicidal peptides active against many Gram-negative and Gram-positive bacteria, fungi, and enveloped viruses, containing three pairs of intramolecular disulfide bonds. On the basis of their size and pattern of disulfide 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. 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.