| Beta defensin | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 | |||||||||
| Identifiers | |||||||||
| Symbol | Defensin_beta | ||||||||
| Pfam | PF00711 | ||||||||
| InterPro | IPR001855 | ||||||||
| SCOP2 | 1bnb /SCOPe /SUPFAM | ||||||||
| OPM superfamily | 54 | ||||||||
| OPM protein | 1ut3 | ||||||||
| |||||||||
Beta defensins are a family of vertebratedefensins. The beta defensins areantimicrobial peptides implicated in the resistance of epithelial surfaces to microbial colonization.
Defensins are 2 to 6 kDa, cationic, microbicidal peptides active against many Gram-negative and Gram-positive bacteria, fungi, and enveloped viruses,[1] containing three pairs of intramolecular disulfide bonds. On the basis of their size and pattern of disulfide bonding, mammalian defensins are classified intoalpha, beta andtheta categories. 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).
Human, rabbit and guinea-pig beta-defensins, as well as human beta-defensin-2 (hBD2), induce the activation and degranulation of mast cells, resulting in the release of histamine and prostaglandin D2.[2]
β-defensins are coding for genes which impact the function of theinnate immune system.[3] These genes are responsible for production ofantimicrobial peptides found inwhite blood cells such asmacrophages,granulocytes andNK-cells, β-defensins are also found inepithelial cells.[4]Single-nucleotide polymorphisms (SNPs) are found in genes coding for β-defensins.[5] The presences ofSNPs are lower in the coding regions compared to non-coding regions.[5] The appearance of SNPs in the coding region will highly likely affecting the resistance against infections through changes in the protein sequences which will give rise to different biological functions.[5]
Receptors such astoll-like receptors (TLR) andnod-like receptors (NLR) will activate theimmune system by binding ofligands such aslipopolysaccharides andpeptidoglycan.[6]Toll-like receptors are expressed in intestinal epithelial cells[7] orantigen presenting cells (APCs) such asdendritic cells,B-lymphocytes andmacrophages.[6] When the receptors are activated acascade reaction will take place and substances such ascytokines andantimicrobial peptides[8] will be released.[6]
β-defensins are cationic and can therefore interact with themembrane of invading microbes, which are negative due tolipopolysaccharides (LPS) andlipoteichoic acid (LTA) found in thecell membrane.[1] The peptides have higher affinity to the binding site compared to Ca2+ and Mg2+ ions.[5] The peptides will therefore exchange place with those ions, thus affecting the stability of the membrane.[5] The peptides have a greater size compared with the ions which cause changes in the membrane structure.[5] Due to changes in theelectric potential, peptides will pass across the membrane and thus aggregate intodimers.[9] Pore complex will be created as a result of breaking thehydrogen bonds between theamino acids in the terminal end of the strands connecting defensins monomers.[9] Formation of pore complex will cause membranedepolarization andcell lysis.[5]
Defensins not only have the ability to strengthen theinnate immune system but can also enhance theadaptive immune system bychemotaxis ofmonocytes,T-lymphocytes,dendritic cells andmast cells to the infection site.[5] Defensins will also improve the capacity ofmacrophage phagocytosis.[5]
β-defensins are classified in three classes and avian β-defensins constitute for one of the classes.[3] This division is based on Zhang's classification and both the length, thehomology of thepeptides and thegene structure are factors affecting the classification.[9]
Avian β-defensins are separated in avianheterophiles and non-heterophiles. Avian heterophiles can be divided into two sub-classes, depending on the number of present homologous residues in thegenome.[9]
Avian heterophiles lack protective oxidative mechanisms, such assuperoxide andmyeloperoxidase, making non-oxidative mechanisms, such aslysosomes and cationic peptides, even more important.[9]
β-defensins genes are found across the vertebrates, including mammals, reptiles, birds and fish.[10] The fact that alpha and theta defensins are absent in older vertebrates, like birds and fishes, indicates that defensins must have evolved from the same ancestral gene coding for β-defensins.[11] Indeed, these defensins of this superfamily are related to the 'big defensins' which are found in invertebrate animals, indicating even earlier origins.[10]
In 2001, it was thought that β-defensins were similar to the ancestral defensin from a comparison of sequences of β-defensins,α-defensins andinsect defensins.[12] Subsequent structural analyses have suggested that the β-defensins, α-defensins,θ-defensins and big defensins share an evolutionary origin, but are separate to the defensins found in insects, fungi and plants.[13]
In addition to other antimicrobial defensins, there are related defensin-like proteins with have evolved other functions. These include toxins found in snakes (e.g.crotamine), bearded lizards and platypus.[14]
The first beta-defensin discovered was Tracheal Antimicrobial Peptide, found in the bovine airway in 1991.[15] The first human beta-defensin, HBD1, was discovered in 1995,[2] followed by the HBD2 in 1997.[16]
DEFB1;DEFB103A;DEFB105A;DEFB105B;DEFB106;DEFB108B;DEFB109;DEFB110;DEFB111;DEFB114;DEFB130;DEFB136;DEFB4;SPAG11A;