Drosocin is a 19-residue long
antimicrobial peptide
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 a ...
(AMP) of flies first isolated in the fruit fly ''
Drosophila melanogaster
''Drosophila melanogaster'' is a species of fly (the taxonomic order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the "vinegar fly" or "pomace fly". Starting with Ch ...
'', and later shown to be conserved throughout the genus ''
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 ...
''.
Drosocin is regulated by the
NF-κB
Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a protein complex that controls transcription of DNA, cytokine production and cell survival. NF-κB is found in almost all animal cell types and is involved in cellular ...
Imd signalling pathway in the fly.
The ''Drosocin'' gene encodes two peptides: its namesake Drosocin peptide and a second peptide called Buletin.
Structure and function
Drosocin is primarily active against
Gram-negative bacteria
Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wall ...
. The peptide is
proline
Proline (symbol Pro or P) is an organic acid classed as a proteinogenic amino acid (used in the biosynthesis of proteins), although it does not contain the amino group but is rather a secondary amine. The secondary amine nitrogen is in the prot ...
-rich with proline-
arginine
Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) and both the am ...
repeats, as well a critical
threonine
Threonine (symbol Thr or T) is an amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH form under biological conditions), a carboxyl group (which is in the deprotonated −COOâ ...
residue. This threonine is ''O''-
glycosylated
Glycosylation is the reaction in which a carbohydrate (or 'glycan'), i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule (a glycosyl acceptor) in order to form a glycoconjugate. In biology (but not alw ...
, which is required for antimicrobial activity.
This ''O''-glycosylation can be performed either by mono- or disaccharides, which have different activity spectra.
Like the antimicrobial peptides
pyrrhocoricin and
abaecin, drosocin binds to bacterial DnaK, inhibiting cell machinery and replication.
The action of these drosocin-like peptides is potentiated by the presence of pore-forming peptides, which facilitates the entry of drosocin-like peptides into the bacterial cell.
Proline-rich peptides such as drosocin can also bind to microbe
ribosome
Ribosomes ( ) are macromolecular machines, found within all cells, that perform biological protein synthesis (mRNA translation). Ribosomes link amino acids together in the order specified by the codons of messenger RNA (mRNA) molecules to ...
s, preventing
protein translation
In molecular biology and genetics, translation is the process in which ribosomes in the cytoplasm or endoplasmic reticulum synthesize proteins after the process of transcription of DNA to RNA in the cell's nucleus. The entire process is ...
.
In the absence of pore-forming peptides, the related AMP pyrrhocoricin is taken into the bacteria by the action of uptake permeases.
In ''Drosophila melanogaster'' the ''Drosocin'' gene is specifically important for the fly defense against infection by ''
Enterobacter cloacae
''Enterobacter cloacae'' is a clinically significant Gram-negative, facultatively-anaerobic, rod-shaped bacterium.
Microbiology
In microbiology labs, ''E. cloacae'' is frequently grown at 30 °C on nutrient agar or at 35 °C in tr ...
'' bacteria,
[ supporting previous ''in vitro'' work showing Drosocin is active against ''E. cloacae''.
The ''Drosocin'' gene of '']Drosophila neotestacea
''Drosophila neotestacea'' is a member of the ''testacea'' species group of ''Drosophila''. Testacea species are specialist fruit flies that breed on the fruiting bodies of mushrooms. These flies will choose to breed on psychoactive mushrooms s ...
'' uniquely encodes tandem repeats of ''Drosocin ''mature peptides between cleavage sites. As a result, a single protein gets chopped up into multiple Drosocin peptides.
Molecular structure
The bolded threonine residue acts as a site for O-glycosylation, also found in the AMPs abaecin and pyrrhocoricin. The underlined PRP motifs are key to the binding of such peptides to the DnaK proteins of bacteria.
Further reading
Drosocin - UniProtKB - P36193 (DROS_DROME)
References
{{Reflist
Drosophila
Insect immunity
Antimicrobial peptides