| Drosocin | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 Drosocin of
Drosophila melanogaster | |||||||||
| Identifiers | |||||||||
| Symbol | Drosocin, Dro or Drc | ||||||||
| Pfam | DIM | ||||||||
| |||||||||
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
- ^ a b Bulet P, Dimarcq JL, Hetru C, Lagueux M, Charlet M, Hegy G, et al. (July 1993). "A novel inducible antibacterial peptide of Drosophila carries an O-glycosylated substitution". The Journal of Biological Chemistry. 268 (20): 14893–14897. doi: 10.1016/S0021-9258(18)82417-6. PMID 8325867.
- ^ a b 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. Bibcode: 2016BMCEE..16..228H. doi: 10.1186/s12862-016-0805-y. PMC 5078906. PMID 27776480.
- ^ a b Hanson MA, Kondo S, Lemaitre B (June 2022). "Drosophila immunity: the Drosocin gene encodes two host defence peptides with pathogen-specific roles". Proceedings. Biological Sciences. 289 (1977): 20220773. doi: 10.1098/rspb.2022.0773. PMC 9233930. PMID 35730150.
- ^ 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): 11342–11347. Bibcode: 1998PNAS...9511342U. doi: 10.1073/pnas.95.19.11342. PMC 21644. PMID 9736738.
- ^ a b Bikker FJ, Kaman-van Zanten WE, de Vries-van de Ruit AM, Voskamp-Visser I, van Hooft PA, Mars-Groenendijk RH, et al. (September 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. PMID 17062012. S2CID 41618771.
- ^ 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): 2463–2479. doi: 10.1016/j.jmb.2013.03.041. PMID 23562829.
- ^ Florin T, Maracci C, Graf M, Karki P, Klepacki D, Berninghausen O, et al. (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.
- ^ Koller TO, Morici M, Berger M, Safdari HA, Lele DS, Beckert B, Kaur KJ, Wilson DN (2023-03-30). "Structural basis for translation inhibition by the glycosylated drosocin peptide". Nature Chemical Biology. 19 (9): 1072–1081. doi: 10.1038/s41589-023-01293-7. ISSN 1552-4469. PMC 10449632. PMID 36997646.
- ^ Rahnamaeian M, Cytryńska M, Zdybicka-Barabas A, Dobslaff K, Wiesner J, Twyman RM, et al. (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.
- ^ 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): 2754–2762. doi: 10.1128/AAC.02565-13. PMC 3993218. PMID 24590485.
- ^ Hanson MA, Dostálová A, Ceroni C, Poidevin M, Kondo S, Lemaitre B (February 2019). "Synergy and remarkable specificity of antimicrobial peptides in vivo using a systematic knockout approach". eLife. 8: e44341. doi: 10.7554/eLife.44341. PMC 6398976. PMID 30803481.
- ^ Bulet P, Urge L, Ohresser S, Hetru C, Otvos L (May 1996). "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. doi: 10.1111/j.1432-1033.1996.0064q.x. PMID 8665953.
- ^ Casteels-Josson K, Capaci T, Casteels P, Tempst P (April 1993). "Apidaecin multipeptide precursor structure: a putative mechanism for amplification of the insect antibacterial response". The EMBO Journal. 12 (4): 1569–1578. doi: 10.1002/j.1460-2075.1993.tb05801.x. PMC 413370. 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
| Drosocin | |||||||||
|---|---|---|---|---|---|---|---|---|---|
|
Drosocin of
Drosophila melanogaster | |||||||||
| Identifiers | |||||||||
| Symbol | Drosocin, Dro or Drc | ||||||||
| Pfam | DIM | ||||||||
| |||||||||
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
- ^ a b Bulet P, Dimarcq JL, Hetru C, Lagueux M, Charlet M, Hegy G, et al. (July 1993). "A novel inducible antibacterial peptide of Drosophila carries an O-glycosylated substitution". The Journal of Biological Chemistry. 268 (20): 14893–14897. doi: 10.1016/S0021-9258(18)82417-6. PMID 8325867.
- ^ a b 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. Bibcode: 2016BMCEE..16..228H. doi: 10.1186/s12862-016-0805-y. PMC 5078906. PMID 27776480.
- ^ a b Hanson MA, Kondo S, Lemaitre B (June 2022). "Drosophila immunity: the Drosocin gene encodes two host defence peptides with pathogen-specific roles". Proceedings. Biological Sciences. 289 (1977): 20220773. doi: 10.1098/rspb.2022.0773. PMC 9233930. PMID 35730150.
- ^ 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): 11342–11347. Bibcode: 1998PNAS...9511342U. doi: 10.1073/pnas.95.19.11342. PMC 21644. PMID 9736738.
- ^ a b Bikker FJ, Kaman-van Zanten WE, de Vries-van de Ruit AM, Voskamp-Visser I, van Hooft PA, Mars-Groenendijk RH, et al. (September 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. PMID 17062012. S2CID 41618771.
- ^ 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): 2463–2479. doi: 10.1016/j.jmb.2013.03.041. PMID 23562829.
- ^ Florin T, Maracci C, Graf M, Karki P, Klepacki D, Berninghausen O, et al. (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.
- ^ Koller TO, Morici M, Berger M, Safdari HA, Lele DS, Beckert B, Kaur KJ, Wilson DN (2023-03-30). "Structural basis for translation inhibition by the glycosylated drosocin peptide". Nature Chemical Biology. 19 (9): 1072–1081. doi: 10.1038/s41589-023-01293-7. ISSN 1552-4469. PMC 10449632. PMID 36997646.
- ^ Rahnamaeian M, Cytryńska M, Zdybicka-Barabas A, Dobslaff K, Wiesner J, Twyman RM, et al. (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.
- ^ 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): 2754–2762. doi: 10.1128/AAC.02565-13. PMC 3993218. PMID 24590485.
- ^ Hanson MA, Dostálová A, Ceroni C, Poidevin M, Kondo S, Lemaitre B (February 2019). "Synergy and remarkable specificity of antimicrobial peptides in vivo using a systematic knockout approach". eLife. 8: e44341. doi: 10.7554/eLife.44341. PMC 6398976. PMID 30803481.
- ^ Bulet P, Urge L, Ohresser S, Hetru C, Otvos L (May 1996). "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. doi: 10.1111/j.1432-1033.1996.0064q.x. PMID 8665953.
- ^ Casteels-Josson K, Capaci T, Casteels P, Tempst P (April 1993). "Apidaecin multipeptide precursor structure: a putative mechanism for amplification of the insect antibacterial response". The EMBO Journal. 12 (4): 1569–1578. doi: 10.1002/j.1460-2075.1993.tb05801.x. PMC 413370. 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.