Beta-defensin 2 (BD-2) also known as skin-antimicrobial peptide 1 (SAP1) is a peptide that in humans is encoded by the DEFB4 (defensin, beta 4) gene. [3]
Human beta-defensin-2 (hBD-2) is a cysteine-rich cationic low molecular weight antimicrobial peptide discovered in lesional skin.
hBD-2 is a protein whose primary structure is made by 64 aminoacids. At concentrations ≤2.4 mM, hBD-2 is monomeric. [4] The structure is amphiphilic with a nonuniform surface distribution of positive charge and contains several key structural elements, including a triple-stranded, antiparallel beta sheet with strands 2 and 3 in a beta hairpin conformation. The determination of other structural elements depends on the technique used. When X-ray crystallography is used an alpha helix can be observed at the N-terminal end of the protein (PDB codes: 1fd3 , 1fd4 , and 6cs9 ). When using NMR this alpha-helix does not appear (PDB code: 1e4q ), however this structure was determined using a truncated version of hBD-2 which was missing the initial 4 amino acids, and may be the reason for the discrepancy.
Defensins form a family of microbicidal and cytotoxic peptides made by neutrophils. Members of the defensin family are highly similar in protein sequence. Beta-defensin 2 is an antibiotic peptide which is locally regulated by inflammation. [5]
Human beta-defensin 2 is produced by a number of epithelial cells and exhibits potent antimicrobial activity against Gram-negative bacteria and Candida , but not Gram-positive S. aureus . It has been speculated that beta-defensin 2 may contribute to the infrequency of Gram-negative infections on skin and lung tissue. [6]
hBD-2 represents the first human defensin that is produced following stimulation of epithelial cells by contact with microorganisms such as P. aeruginosa or cytokines such as TNF-alpha and IL-1 beta. The HBD-2 gene and protein are locally expressed in keratinocytes associated with inflammatory skin lesions. It is intriguing to speculate that HBD-2 is a dynamic component of the local epithelial defense system of the skin and respiratory tract having a role to protect surfaces from infection, and providing a possible reason why skin and lung infections with Gram-negative bacteria are rather rare. [6]
Although this protein doesn’t have any antibacterial activity against Gram-positive bacteria, there is a study showing that there is a synergy between hBD-2 and other proteins. [7] One example of this synergistic effect is with epiP, a protein segregated by some strains of S. epidermidis . hBD2, holding hands with epiP, is capable of killing S. aureus , a Gram-positive bacteria responsible of human diseases.
Defensins are small cysteine-rich cationic proteins across cellular life, including vertebrate and invertebrate animals, plants, and fungi. They are host defense peptides, with members displaying either direct antimicrobial activity, immune signaling activities, or both. They are variously active against bacteria, fungi and many enveloped and nonenveloped viruses. They are typically 18-45 amino acids in length, with three or four highly conserved disulphide bonds.
Antimicrobial peptides (AMPs), also called host defence peptides (HDPs) are part of the innate immune response found among all classes of life. Fundamental differences exist between prokaryotic and eukaryotic cells that may represent targets for antimicrobial peptides. These peptides are potent, broad spectrum antimicrobials which demonstrate potential as novel therapeutic agents. Antimicrobial peptides have been demonstrated to kill Gram negative and Gram positive bacteria, enveloped viruses, fungi and even transformed or cancerous cells. Unlike the majority of conventional antibiotics it appears that antimicrobial peptides frequently destabilize biological membranes, can form transmembrane channels, and may also have the ability to enhance immunity by functioning as immunomodulators.
Paneth cells are cells in the small intestine epithelium, alongside goblet cells, enterocytes, and enteroendocrine cells. Some can also be found in the cecum and appendix. They are located below the intestinal stem cells in the intestinal glands and the large eosinophilic refractile granules that occupy most of their cytoplasm.
The C3a receptor also known as complement component 3a receptor 1 (C3AR1) is a G protein-coupled receptor protein involved in the complement system.
Cathelicidin antimicrobial peptide (CAMP) is an antimicrobial peptide encoded in the human by the CAMP gene. The active form is LL-37. In humans, CAMP encodes the peptide precursor CAP-18, which is processed by proteinase 3-mediated extracellular cleavage into the active form LL-37.
Alpha defensins are a family of mammalian defensin peptides of the alpha subfamily. They are also known as cryptdins and are produced within the small bowel. Cryptdin is a portmanteau of crypt and defensin.
Beta defensins are a family of vertebrate defensins. The beta defensins are antimicrobial peptides implicated in the resistance of epithelial surfaces to microbial colonization.
Beta-defensin 1 is a protein that in humans is encoded by the DEFB1 gene.
Trefoil factor 3 is a protein that in humans is encoded by the TFF3 gene.
Beta-defensin 103 is a protein that in humans is encoded by the DEFB103A gene.
Arthropod defensins are a family defensin proteins found in mollusks, insects, and arachnids. These cysteine-rich antibacterial peptides are primarily active against Gram-positive bacteria and fungi in vitro. However Drosophila fruit flies mutant for the fly defensin were more susceptible to infection by the Gram-negative bacteria Providencia burhodogranariea, and resisted infection against Gram-positive bacteria like wild-type flies. It remains to be seen how in vitro activity relates to in vivo function. Mutants for the defensin-like antimicrobial peptide Drosomycin were more susceptible to fungi, validating a role for defensin-like peptides in anti-fungal defence.
Defensin, alpha 5 (DEFA5) also known as human alpha defensin 5 (HD5) is a protein that in humans is encoded by the DEFA5 gene. DEFA5 is expressed in the Paneth cells of the ileum.
Beta-defensin 104 is a protein that in humans is encoded by the DEFB104A gene.
Beta-defensin 106 is a protein that in humans is encoded by the DEFB106A gene.
Beta-defensin 118 is a protein that in humans is encoded by the DEFB118 gene.
Beta-defensin 127 is a protein that in humans is encoded by the DEFB127 gene.
Beta-defensin 105 is a protein that is encoded by the DEFB105A gene in humans.
Beta-defensin 129 is a protein that in humans is encoded by the DEFB129 gene.
Defensin, alpha 6 (DEFA6) also known as human alpha defensin 6 (HD6) is a human protein that is encoded by the DEFA6 gene. DEFA6 is expressed in the Paneth cells of the ileum.
Theta-defensins are a family of mammalian antimicrobial peptides. They are found in non-human 'Old World' primates, but not in human, gorilla, bonobo, and chimpanzee.
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