Arthropod defensin
Protein family
From Wikipedia, the free encyclopedia
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.[2][3][4][5][6] 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.[7] 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.[7]
Structure
Arthropod defensin peptides range in length from 38 to 51 amino acids. There are six conserved cysteines all involved in intrachain disulfide bonds. Studies have shown that the cysteine-bridge disulfide bonds are not required for antimicrobial activity,[8] similar to findings in mammalian defensins.[9] Furthermore, it was also shown that the N-terminal helix region in arthropod or insect defensins is also not required for antimicrobial activity of these peptides.[8]
A schematic representation of peptides from the arthropod defensin family is shown below.
+----------------------------+
| |
xxCxxxxxxxxxxxxxxCxxxCxxxxxxxxxCxxxxxCxCxx
| | | |
+---|---------------+ |
+-----------------+
'C': conserved cysteine involved in a disulfide bond.
Relation to other defensins
Sequence similarities have been reported between the arthropod defensins and mammalian defensins.[10][2] However it appears that defensins of vertebrates, arthropods, plants, and fungi arose independently.[11] This is supported by 3D structural differences between arthropod defensins and vertebrate beta defensins.[12] However structural similarities exist between these defensins, notably in two structural motifs termed "C6" and "C8". This has prompted a higher "cis-" or "tras-" defensin classification system wherein the structural relationships of the shared motifs is used to delineate defensin similarities.[11]
Activity against non-microbial cells
Defensins of mammals display anti-cancer activities in vitro,[13] and down-regulation of human beta-defensin 1 is associated with increased risk of prostate cancer and clear-cell carcinomas.[14] The first in vivo anti-cancer functions for defensin came from Drosophila studies, which showed that the Drosophila defensin attacks tumor cells, and that flies lacking defensin had greater tumor growth in a cancer disease model.[15][16]
Overactive immune signalling is also implicated in age-associated neurodegeneration,[17] and overexpression of defensin leads to increased degradation of brain tissue.[18]
