Drosocin is a 19-residue long antimicrobial peptide (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 ...

'', 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 s ...

''. 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 wa ...

. The peptide is proline-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 a ...

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 −COO ...

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 ...

, 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 Pyrrhocoricin is a 20-residue long antimicrobial peptide of the firebug ''Pyrrhocoris apterus''. Structure and function Pyrrhocoricin is primarily active against Gram-negative bacteria. The peptide is proline-rich with proline-arginine repeat ...

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 ribosomes, 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'' 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 ...

'' uniquely encodes tandem repeats of ''Drosocin ''mature peptides between cleavage sites. As a result, a single protein gets chopped up into multiple Drosocin peptides. This tandem repeat structure is also found in the honeybee AMP apidaecin, and is hypothesized as an evolutionary mechanism to increase the speed of the immune response and AMP production.

Molecular structure

The bolded threonine residue acts as a site for O-glycosylation, also found in the AMPs abaecin and

. The underlined PRP motifs are key to the binding of such peptides to the DnaK proteins of bacteria. ''D. melanogaster drosocin: GKPRPYSPRPTSHPRPIRV''

References

{{Reflist Drosophila Insect immunity Antimicrobial peptides

Structure and function

Molecular structure

Further reading

References