Drosocin


Drosocin is a 19-residue long antimicrobial peptide of flies first isolated in the fruit fly Drosophila melanogaster, and later shown to be conserved throughout the genus Drosophila. Drosocin is regulated by the NF-κB Imd signalling pathway in the fly.

Structure and function

Drosocin is primarily active against Gram-negative bacteria. The peptide is proline-rich with proline-arginine repeats, as well a critical threonine residue. This threonine is O-glycosylated, 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 baceterial cell. Proline-rich peptides such as drosocin can also bind to microbe ribosomes, preventing protein translation. In the absence of pore-forming peptides, the related AMP pyrrhocoricin is taken into the bacteria by the action of uptake permeases.
The Drosocin gene of Drosophila neotestacea 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 pyrrhocoricin. The underlined PRP motifs are key to the binding of such peptides to the DnaK proteins of bacteria.
D. melanogaster drosocin: GKPRPYSPRPTSHPRPIRV