Structural and positional studies of the antimicrobial peptide brevinin-1BYa in membrane-mimetic environments

PB Timmons, D O'Flynn, JM Conlon, C Hewage

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Brevinin-1BYa (FLPILASLAAKFGPKLFCLVTKKC), first isolated from skin secretions of the foothill yellow-legged frog Rana boylii, shows broad-spectrum activity, being particularly effective against opportunistic yeast pathogens. The structure of brevinin-1BYa was investigated in various solution and membrane-mimicking environments by proton nuclear magnetic resonance ( 1H-NMR) spectroscopy and molecular modelling. The peptide does not possess a secondary structure in aqueous solution. In a 33% 2,2,2-trifluoroethanol (TFE-d 3)-H 2O solvent mixture, as well as in membrane-mimicking sodium dodecyl sulfate and dodecylphosphocholine micelles, the peptide's structure is characterised by a flexible helix-hinge-helix motif, with the hinge located at the Gly 13/Pro 14 residues, and the two α-helices extending from Pro 3 to Phe 12 and from Pro 14 to Thr 21. Positional studies involving the peptide in sodium dodecyl sulfate and dodecylphosphocholine micelles using 5-doxyl-labelled stearic acid and manganese chloride paramagnetic probes show that the peptide's helical segments lie parallel to the micellar surface, with the residues on the hydrophobic face of the amphipathic helices facing towards the micelle core and the hydrophilic residues pointing outwards, suggesting that the peptide exerts its biological activity by a non–pore-forming mechanism.

LanguageEnglish
Article numbere3208
JournalJournal of Peptide Science
Volume25
Issue number11
DOIs
Publication statusPublished - 12 Nov 2019

Fingerprint

Membranes
Micelles
Peptides
Hinges
Sodium Dodecyl Sulfate
Magnetic Resonance Spectroscopy
Nuclear magnetic resonance
Trifluoroethanol
Ranidae
Molecular modeling
Polytetrafluoroethylene
Pathogens
Bioactivity
Anura
Yeast
Nuclear magnetic resonance spectroscopy
Protons
Skin
Yeasts
dodecylphosphocholine

Keywords

  • AMP
  • brevinin
  • modelling
  • NMR
  • peptides

Cite this

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abstract = "Brevinin-1BYa (FLPILASLAAKFGPKLFCLVTKKC), first isolated from skin secretions of the foothill yellow-legged frog Rana boylii, shows broad-spectrum activity, being particularly effective against opportunistic yeast pathogens. The structure of brevinin-1BYa was investigated in various solution and membrane-mimicking environments by proton nuclear magnetic resonance ( 1H-NMR) spectroscopy and molecular modelling. The peptide does not possess a secondary structure in aqueous solution. In a 33{\%} 2,2,2-trifluoroethanol (TFE-d 3)-H 2O solvent mixture, as well as in membrane-mimicking sodium dodecyl sulfate and dodecylphosphocholine micelles, the peptide's structure is characterised by a flexible helix-hinge-helix motif, with the hinge located at the Gly 13/Pro 14 residues, and the two α-helices extending from Pro 3 to Phe 12 and from Pro 14 to Thr 21. Positional studies involving the peptide in sodium dodecyl sulfate and dodecylphosphocholine micelles using 5-doxyl-labelled stearic acid and manganese chloride paramagnetic probes show that the peptide's helical segments lie parallel to the micellar surface, with the residues on the hydrophobic face of the amphipathic helices facing towards the micelle core and the hydrophilic residues pointing outwards, suggesting that the peptide exerts its biological activity by a non–pore-forming mechanism.",
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Structural and positional studies of the antimicrobial peptide brevinin-1BYa in membrane-mimetic environments. / Timmons, PB; O'Flynn, D; Conlon, JM; Hewage, C.

In: Journal of Peptide Science, Vol. 25, No. 11, e3208, 12.11.2019.

Research output: Contribution to journalArticle

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AU - O'Flynn, D

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AB - Brevinin-1BYa (FLPILASLAAKFGPKLFCLVTKKC), first isolated from skin secretions of the foothill yellow-legged frog Rana boylii, shows broad-spectrum activity, being particularly effective against opportunistic yeast pathogens. The structure of brevinin-1BYa was investigated in various solution and membrane-mimicking environments by proton nuclear magnetic resonance ( 1H-NMR) spectroscopy and molecular modelling. The peptide does not possess a secondary structure in aqueous solution. In a 33% 2,2,2-trifluoroethanol (TFE-d 3)-H 2O solvent mixture, as well as in membrane-mimicking sodium dodecyl sulfate and dodecylphosphocholine micelles, the peptide's structure is characterised by a flexible helix-hinge-helix motif, with the hinge located at the Gly 13/Pro 14 residues, and the two α-helices extending from Pro 3 to Phe 12 and from Pro 14 to Thr 21. Positional studies involving the peptide in sodium dodecyl sulfate and dodecylphosphocholine micelles using 5-doxyl-labelled stearic acid and manganese chloride paramagnetic probes show that the peptide's helical segments lie parallel to the micellar surface, with the residues on the hydrophobic face of the amphipathic helices facing towards the micelle core and the hydrophilic residues pointing outwards, suggesting that the peptide exerts its biological activity by a non–pore-forming mechanism.

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