Defensin
Defensin | |
---|---|
Identifiers | |
Symbol | Defensin |
Pfam clan | CL0075 |
OPM superfamily | 54 |
OPM protein | 6cs9 |
Defensins are small
In animals, they are produced by cells of the
Varieties
The name 'defensin' was coined in the mid-1980s, though the proteins have been called 'Cationic Antimicrobial Proteins,' 'Neutrophil peptides,' 'Gamma thionins' amongst others.[6]
Proteins called 'defensins' are not all evolutionarily related to one another.[7] Instead fall into two broad superfamilies, each of which contains multiple families.[7][8] One superfamily, the trans-defensins, contains the defensins found in humans and other vertebrates,[9][10] as well as some invertebrates.[11][12] The other superfamily, cis-defensins, contains the defensins found in invertebrates, plants, and fungi.[13][14][15] The superfamilies and families are determined by the overall tertiary structure, and each family usually has a conserved pattern of disulphide bonds.[9][16] All defensins form small and compact folded structures, typically with a high positive charge, that are highly stable due to the multiple disulphide bonds. In all families, the underlying genes responsible for defensin production are highly polymorphic.[citation needed]
Trans-defensins
Vertebrate defensins are primarily α-defensins and β-defensins. Some primates additionally have the much smaller θ-defensins. In general, both α- and β-defensins are encoded by two-exon genes, where the first exon encodes for a hydrophobic leader sequence (removed after translation) and the cysteine-rich sequence (the mature peptide). The disulfide linkages formed by the cysteines have been suggested to be essential for activities related to innate immunity in mammals, but are not necessarily required for antimicrobial activity.[17][18] Theta defensins form a single beta-hairpin structure and represent a distinct group. Only alpha and beta-defensins are expressed in humans.[19]
Type | Gene Symbol | Gene Name | Protein Name | Description |
---|---|---|---|---|
α-defensins | DEFA1 | Defensin, alpha 1 | Neutrophil defensin 1 | Are expressed primarily in Paneth cells of the small intestine, where they may regulate and maintain microbial balance in the intestinal lumen.
|
DEFA1B | Defensin, alpha 1B | Defensin, alpha 1 | ||
DEFA3 | Defensin, alpha 3, neutrophil-specific | Neutrophil defensin 3 | ||
DEFA4 | Defensin, alpha 4, corticostatin | Neutrophil defensin 4 | ||
DEFA5 | Defensin, alpha 5, Paneth cell-specific | Defensin-5 | ||
DEFA6 | Defensin, alpha 6, Paneth cell-specific | Defensin-6 | ||
β-defensins | DEFB1
|
Defensin, beta 1 | Beta-defensin 1 | Are the most widely distributed, being secreted by epithelial cells of many kinds. For example, they can be found on the tongue, skin, cornea, salivary glands, kidneys, esophagus, and respiratory tract. It has been suggested (but also challenged) that some of the pathology of cystic fibrosis arises from the inhibition of β-defensin activity on the epithelial surfaces of the lungs and trachea due to higher salt content.
|
DEFB2 | Defensin, beta 2 | Beta-defensin 2 | ||
DEFB3 | Defensin, beta 3 | Beta-defensin 3 | ||
DEFB103A | Defensin, beta 103B | Beta-defensin 103 | ||
... | ... | ... | ||
DEFB106A | Defensin, beta 106A | Beta-defensin 106A | ||
DEFB106 B
|
Defensin, beta 106B | Beta-defensin 106B | ||
DEFB107B | Defensin, beta 107A | Beta-defensin 107 | ||
DEFB110 | Defensin, beta 110 | Beta-defensin 110 | ||
... | ... | ... | ||
DEFB136 | Defensin, beta 136 | Beta-defensin 136 | ||
θ-defensins | DEFT1P | Defensin, theta 1 pseudogene | not expressed in humans | Are rare, and thus far have been found only in the leukocytes of the |
Although the most well-studied defensins are from vertebrates, a family of trans-defensins called 'big defensins' are found in
Cis-defensins
Plant defensins were discovered in 1990 and have subsequently been found in most plant tissues with antimicrobial activities, with both antifungal and antibacterial examples.[25] They have been identified in all major groups of vascular plants, but not in ferns, mosses or algae.[25]
Bacterial defensins have also been identified, but are by far the least studied. They include variants with only four cysteines, whereas defensins from eukaryote defensins almost all have six or eight.[28]
Related defensin-like proteins
In addition to the defensins involved in host defence, there are a number of related Defensin-Like Peptides (DLPs) that have evolved to have other activities.
Toxins
There appear to have been multiple evolutionary recruitments of defensins to be toxin proteins used in the venoms of animals;
Signalling
In vertebrates, some α- and β-defensins are involved in signalling between the
Enzyme inhibitors
Some antimicrobial defensins also have enzyme inhibitory activity, and some DLPs function primarily as enzyme inhibitors, acting as antifeedants (discouraging animals from eating them).[36][37][38]
Function
In immature
In human breast milk, defensins play a central role in neonate immunity.[39]
The human genome contains theta-defensin genes, but they have a premature
Also interesting is the effect of alpha-defensins on the
They have generally been considered to contribute to mucosal health; however, it is possible that these peptides can be considered biological factors that can be upregulated by bioactive compounds present in human breast milk. In this sense, the intestinal production of antimicrobial peptides as hBD2 and hBD4 by trefoil from milk might play an important role on neonate colonization, thereby enhancing the immune response of newborns against pathogens with which they may come in contact.[39][43]
Pathology
The alpha defensin peptides are increased in chronic inflammatory conditions.
Alpha defensin are increased in several cancers, including colorectal cancer.[44]
An imbalance of defensins in the skin may contribute to acne.[45]
A reduction of ileal defensins may predispose to Crohn's disease.[46][47]
In one small study, a significant increase in alpha defensin levels was detected in T cell lysates of schizophrenia patients; in discordant twin pairs, unaffected twins also had an increase, although not as high as that of their ill siblings. The authors suggested that alpha-defensin levels might prove a useful marker for schizophrenia risk.[48]
Defensins are found in the human skin during inflammatory conditions like psoriasis[49] and also during wound healing.
Applications
Defensins
At present, the widespread spread of antibiotic resistance requires the search and development of new antimicrobial drugs. From this point of view, defensins (as well as antimicrobial peptides in general) are of great interest. It was shown that defensins have pronounced antibacterial activity against a wide range of pathogens.[50] In addition, defensins can enhance the effectiveness of conventional antibiotics.[50]
Defensin-mimetics
Defensin
See also
- Host defense peptides, to which defensins belong
References
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- ^ "PMX-30063 The First And Only Defensin Mimetic Systemic Antibiotic Drug In Human Clinical Trials". 2008.
- ^ Clinical trial number NCT02324335 for "Phase 2 Study to Evaluate the Safety & Efficacy of Brilacidin Oral Rinse in Patients With Head and Neck Cancer (Brilacidin)" at ClinicalTrials.gov
- ^ "Brilacidin-OM page". Cellceutix. Archived from the original on 2015-02-07. Retrieved 2015-03-02.
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External links
- Defensins Database, Singapore Archived 2008-04-24 at the Wayback Machine
- Innate ( Nonspecific ) Immunity at Western Kentucky University
- UMich Orientation of Proteins in Membranes families/superfamily-56 - Vertebrate defensins and related sea anemone sodium channel toxins
- UMich Orientation of Proteins in Membranes families/superfamily-61 - Defensins from insects and plants and scorpion toxins
- Defensins at the U.S. National Library of Medicine Medical Subject Headings (MeSH)