Drosocin

Drosocin is a 19-residue long antimicrobial peptide (AMP) of flies first isolated in the fruit fly Drosophila melanogaster, and later shown to be conserved throughout the genus Drosophila.[1][2] Drosocin is regulated by the NF-κB Imd signalling pathway in the fly.

Drosocin
The fruit fly, Drosophila melanogaster
Identifiers
SymbolDrosocin, Dro or Drc
PfamDIM

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.[1] This O-glycosylation can be performed either by mono- or disaccharides, which have different activity spectra.[3] Like the antimicrobial peptides pyrrhocoricin and abaecin, drosocin binds to bacterial DnaK, inhibiting cell machinery and replication.[4] 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.[5] Proline-rich peptides such as drosocin can also bind to microbe ribosomes, preventing protein translation.[6] In the absence of pore-forming peptides, the related AMP pyrrhocoricin is taken into the bacteria by the action of uptake permeases.[7]

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.[2] 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.[8]

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.[9]

D. melanogaster drosocin: GKPRPYSPRPTSHPRPIRV

Further reading
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References
  1. Bulet P, Dimarcq JL, Hetru C, Lagueux M, Charlet M, Hegy G, Van Dorsselaer A, Hoffmann JA (July 1993). "A novel inducible antibacterial peptide of Drosophila carries an O-glycosylated substitution". The Journal of Biological Chemistry. 268 (20): 14893–7. PMID 8325867.
  2. Hanson MA, Hamilton PT, Perlman SJ (October 2016). "Immune genes and divergent antimicrobial peptides in flies of the subgenus Drosophila". BMC Evolutionary Biology. 16 (1): 228. doi:10.1186/s12862-016-0805-y. PMC 5078906. PMID 27776480.
  3. Uttenweiler-Joseph S, Moniatte M, Lagueux M, Van Dorsselaer A, Hoffmann JA, Bulet P (September 1998). "Differential display of peptides induced during the immune response of Drosophila: a matrix-assisted laser desorption ionization time-of-flight mass spectrometry study". Proceedings of the National Academy of Sciences of the United States of America. 95 (19): 11342–7. Bibcode:1998PNAS...9511342U. doi:10.1073/pnas.95.19.11342. PMC 21644. PMID 9736738.
  4. Zahn M, Berthold N, Kieslich B, Knappe D, Hoffmann R, Sträter N (July 2013). "Structural studies on the forward and reverse binding modes of peptides to the chaperone DnaK". Journal of Molecular Biology. 425 (14): 2463–79. doi:10.1016/j.jmb.2013.03.041. PMID 23562829.
  5. Rahnamaeian M, Cytryńska M, Zdybicka-Barabas A, Dobslaff K, Wiesner J, Twyman RM, Zuchner T, Sadd BM, Regoes RR, Schmid-Hempel P, Vilcinskas A (May 2015). "Insect antimicrobial peptides show potentiating functional interactions against Gram-negative bacteria". Proceedings. Biological Sciences. 282 (1806): 20150293. doi:10.1098/rspb.2015.0293. PMC 4426631. PMID 25833860.
  6. Florin T, Maracci C, Graf M, Karki P, Klepacki D, Berninghausen O, Beckmann R, Vázquez-Laslop N, Wilson DN, Rodnina MV, Mankin AS (September 2017). "An antimicrobial peptide that inhibits translation by trapping release factors on the ribosome". Nature Structural & Molecular Biology. 24 (9): 752–757. doi:10.1038/nsmb.3439. PMC 5589491. PMID 28741611.
  7. Narayanan S, Modak JK, Ryan CS, Garcia-Bustos J, Davies JK, Roujeinikova A (May 2014). "Mechanism of Escherichia coli resistance to Pyrrhocoricin". Antimicrobial Agents and Chemotherapy. 58 (5): 2754–62. doi:10.1128/AAC.02565-13. PMC 3993218. PMID 24590485.
  8. Casteels-Josson, K; Capaci, T; Casteels, P; Tempst, P (1993). "Apidaecin multipeptide precursor structure: a putative mechanism for amplification of the insect antibacterial response". EMBO J. 12 (4): 1569–78. PMID 8467807.
  9. Zahn, M; Straeter, N (2013). "Crystal structure of the substrate binding domain of E.coli DnaK in complex with metchnikowin (residues 20 to 26)". RCSB PDB. doi:10.2210/pdb4EZS/pdb.
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