Arthropod defensins are a family
defensin proteins found in mollusks, insects, and arachnids. These
cysteine
Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile.
When present as a deprotonated catalytic residue, sometime ...
-rich
antibacterial peptides are primarily active against
Gram-positive bacteria
In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall.
Gram-positive bact ...
and fungi in vitro.
However ''
Drosophila
''Drosophila'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species ...
'' 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
Drosomycin is an antifungal peptide from ''Drosophila melanogaster'' and was the first antifungal peptide isolated from insects. Drosomycin is induced by infection by the Toll signalling pathway, while expression in surface epithelia like the re ...
were more susceptible to fungi, validating a role for defensin-like peptides in anti-fungal defence.
Structure
Arthropod defensin peptides range in length from 38 to 51 amino acids. There are six conserved cysteines all involved in intrachain
disulfide bonds
In biochemistry, a disulfide (or disulphide in British English) refers to a functional group with the structure . The linkage is also called an SS-bond or sometimes a disulfide bridge and is usually derived by the coupling of two thiol groups. In ...
. Studies have shown that the cysteine-bridge disulfide bonds are not required for antimicrobial activity,
similar to findings in mammalian defensins. Furthermore, it was also shown that the
N-terminal
The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the ami ...
helix region in arthropod or insect defensins is also not required for antimicrobial activity of these peptides.
A schematic representation of peptides from the arthropod
defensin
Defensins are small cysteine-rich cationic proteins across cellular life, including vertebrate
Vertebrates () comprise all animal taxa within the subphylum Vertebrata () ( chordates with backbones), including all mammals, birds, reptiles, ...
family is shown below.
+----------------------------+
, ,
, , , ,
+---, ---------------+ ,
+-----------------+
'C': conserved cysteine involved in a disulfide bond.
Relation to other defensins
Sequence similarities have been reported between the arthropod defensins and mammalian defensins.
However it appears that defensins of vertebrates, arthropods, plants, and fungi arose independently.
This is supported by 3D structural differences between arthropod defensins and vertebrate
beta 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.
Defensins are 2-6 kDa, cationic, microbicidal peptides active again ...
s.
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.
Activity against non-microbial cells
Defensins of mammals display anti-cancer activities in vitro,
and down-regulation of human beta-defensin 1 is associated with increased risk of
prostate cancer
Prostate cancer is cancer of the prostate. Prostate cancer is the second most common cancerous tumor worldwide and is the fifth leading cause of cancer-related mortality among men. The prostate is a gland in the male reproductive system that sur ...
and
clear-cell carcinomas.
The first in vivo anti-cancer functions for defensin came from ''
Drosophila
''Drosophila'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species ...
'' studies, which showed that the ''Drosophila'' defensin attacks tumor cells, and that flies lacking defensin had greater tumor growth in a cancer disease model.
Overactive immune signalling is also implicated in age-associated neurodegeneration,
and overexpression of defensin leads to increased degradation of brain tissue.
Notes
Further reading
*
References
*
* - Arthropod defensins in
PROSITE
PROSITE is a protein database. It consists of entries describing the protein families, domains and functional sites as well as amino acid patterns and profiles in them. These are manually curated by a team of the Swiss Institute of Bioinformati ...
(=source of figure)
Defensins
Toxins
Peripheral membrane proteins
Insect immunity
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