Biology:Drosocin
| Drosocin | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 Drosocin of Drosophila melanogaster | |||||||||
| Identifiers | |||||||||
| Symbol | Drosocin, Dro or Drc | ||||||||
| Pfam | DIM | ||||||||
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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.
The Drosocin gene encodes two peptides: its namesake Drosocin peptide and a second peptide called Buletin.[3]
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.[4] Like the antimicrobial peptides pyrrhocoricin and abaecin, drosocin early studies showed it can bind to bacterial DnaK, inhibiting cell machinery and replication.[5][6] However the action of these drosocin-like peptides may instead be to bind to microbe ribosomes, preventing protein translation.[7][8] Proline-rich peptides such as drosocin are potentiated by the presence of pore-forming peptides, which facilitates the entry of drosocin-like peptides into the bacterial cell.[9] In the absence of pore-forming peptides, the related AMP pyrrhocoricin is taken into the bacteria by the action of uptake permeases.[10] In Drosophila melanogaster the Drosocin gene is specifically important for the fly defense against infection by Enterobacter cloacae bacteria,[3][11] supporting previous in vitro work showing Drosocin is active against E. cloacae.[12]
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 or fruit fly Baramicin, and is hypothesized as an evolutionary mechanism to increase the speed of the immune response and AMP production.[13]
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.[5][14]
D. melanogaster drosocin: GKPRPYSPRPTSHPRPIRV
References
- ↑ 1.0 1.1 "A novel inducible antibacterial peptide of Drosophila carries an O-glycosylated substitution". The Journal of Biological Chemistry 268 (20): 14893–14897. July 1993. doi:10.1016/S0021-9258(18)82417-6. PMID 8325867.
- ↑ 2.0 2.1 "Immune genes and divergent antimicrobial peptides in flies of the subgenus Drosophila". BMC Evolutionary Biology 16 (1): 228. October 2016. doi:10.1186/s12862-016-0805-y. PMID 27776480. Bibcode: 2016BMCEE..16..228H.
- ↑ 3.0 3.1 "Drosophila immunity: the Drosocin gene encodes two host defence peptides with pathogen-specific roles". Proceedings. Biological Sciences 289 (1977): 20220773. June 2022. doi:10.1098/rspb.2022.0773. PMID 35730150.
- ↑ "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): 11342–11347. September 1998. doi:10.1073/pnas.95.19.11342. PMID 9736738. Bibcode: 1998PNAS...9511342U.
- ↑ 5.0 5.1 "Evaluation of the antibacterial spectrum of drosocin analogues". Chemical Biology & Drug Design 68 (3): 148–153. September 2006. doi:10.1111/j.1747-0285.2006.00424.x. PMID 17062012.
- ↑ "Structural studies on the forward and reverse binding modes of peptides to the chaperone DnaK". Journal of Molecular Biology 425 (14): 2463–2479. July 2013. doi:10.1016/j.jmb.2013.03.041. PMID 23562829.
- ↑ "An antimicrobial peptide that inhibits translation by trapping release factors on the ribosome". Nature Structural & Molecular Biology 24 (9): 752–757. September 2017. doi:10.1038/nsmb.3439. PMID 28741611.
- ↑ Koller, Timm O.; Morici, Martino; Berger, Max; Safdari, Haaris A.; Lele, Deepti S.; Beckert, Bertrand; Kaur, Kanwal J.; Wilson, Daniel N. (2023-03-30). "Structural basis for translation inhibition by the glycosylated drosocin peptide" (in en). Nature Chemical Biology 19 (9): 1072–1081. doi:10.1038/s41589-023-01293-7. ISSN 1552-4469. PMID 36997646.
- ↑ "Insect antimicrobial peptides show potentiating functional interactions against Gram-negative bacteria". Proceedings. Biological Sciences 282 (1806): 20150293. May 2015. doi:10.1098/rspb.2015.0293. PMID 25833860.
- ↑ "Mechanism of Escherichia coli resistance to Pyrrhocoricin". Antimicrobial Agents and Chemotherapy 58 (5): 2754–2762. May 2014. doi:10.1128/AAC.02565-13. PMID 24590485.
- ↑ "Synergy and remarkable specificity of antimicrobial peptides in vivo using a systematic knockout approach". eLife 8: e44341. February 2019. doi:10.7554/eLife.44341. PMID 30803481.
- ↑ "Enlarged scale chemical synthesis and range of activity of drosocin, an O-glycosylated antibacterial peptide of Drosophila". European Journal of Biochemistry 238 (1): 64–69. May 1996. doi:10.1111/j.1432-1033.1996.0064q.x. PMID 8665953.
- ↑ "Apidaecin multipeptide precursor structure: a putative mechanism for amplification of the insect antibacterial response". The EMBO Journal 12 (4): 1569–1578. April 1993. doi:10.1002/j.1460-2075.1993.tb05801.x. PMID 8467807.
- ↑ 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.
Further reading
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