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][5] 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.[6] Proline-rich peptides such as drosocin can also bind to microbe ribosomes, preventing protein translation.[7] In the absence of pore-forming peptides, the related AMP pyrrhocoricin is taken into the bacteria by the action of uptake permeases.[8]

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.[9]

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.[4][10]

D. melanogaster drosocin: GKPRPYSPRPTSHPRPIRV

Further reading

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. doi:10.1016/S0021-9258(18)82417-6. 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. Bikker, Floris J.; Kaman-van Zanten, Wendy E.; de Vries-van de Ruit, Anne-Marij B. C.; Voskamp-Visser, Ingrid; van Hooft, Peter A. V.; Mars-Groenendijk, Roos H.; de Visser, Peter C.; Noort, Daan (2006). "Evaluation of the antibacterial spectrum of drosocin analogues". Chemical Biology & Drug Design. 68 (3): 148–153. doi:10.1111/j.1747-0285.2006.00424.x. ISSN 1747-0277. PMID 17062012. S2CID 41618771.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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. doi:10.1002/j.1460-2075.1993.tb05801.x. PMC 413370. PMID 8467807.
  10. Zahn, M; Straeter, N (2013). "Crystal structure of the substrate binding domain of E.coli DnaK in complex with metchnikowin (residues 20 to 26)". Protein Data Bank. doi:10.2210/pdb4EZS/pdb.
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