TY - JOUR
T1 - Structural and positional studies of the antimicrobial peptide brevinin-1BYa in membrane-mimetic environments
AU - Timmons, Patrick Brendan
AU - O'Flynn, Donal
AU - Conlon, J. Michael
AU - Hewage, Chandralal M.
N1 - Funding Information:
P.B.T. and D.O.F. share equal authorship of this work. The authors are grateful to University College Dublin for the Research Scholarship to P.B.T. and D.O.F. and would like to acknowledge the funding from Science Foundation Ireland for the NMR spectrometer upgrade. The authors also wish to acknowledge the DJEI/DES/SFI/HEA Irish Centre for High‐End Computing (ICHEC) for the provision of computational facilities and support. Structural coordinates and chemical shifts were deposited in the PDB at RCSB with codes 6G4I, 6G4K, and 6G4U, respectively. Tables of Supporting Information 1 H chemical shift assignments are supplied as .
Funding Information:
P.B.T. and D.O.F. share equal authorship of this work. The authors are grateful to University College Dublin for the Research Scholarship to P.B.T. and D.O.F. and would like to acknowledge the funding from Science Foundation Ireland for the NMR spectrometer upgrade. The authors also wish to acknowledge the DJEI/DES/SFI/HEA Irish Centre for High-End Computing (ICHEC) for the provision of computational facilities and support. Structural coordinates and chemical shifts were deposited in the PDB at RCSB with codes 6G4I, 6G4K, and 6G4U, respectively. Tables of 1H chemical shift assignments are supplied as Supporting Information.
Publisher Copyright:
© 2019 European Peptide Society and John Wiley & Sons, Ltd.
PY - 2019/11/1
Y1 - 2019/11/1
N2 - 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-d3)-H2O 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 Gly13/Pro14 residues, and the two α-helices extending from Pro3 to Phe12 and from Pro14 to Thr21. 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.
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-d3)-H2O 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 Gly13/Pro14 residues, and the two α-helices extending from Pro3 to Phe12 and from Pro14 to Thr21. 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.
KW - AMP
KW - NMR
KW - brevinin
KW - modelling
KW - peptides
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U2 - 10.1002/psc.3208
DO - 10.1002/psc.3208
M3 - Article
C2 - 31721374
AN - SCOPUS:85073826951
SN - 1075-2617
VL - 25
JO - Journal of Peptide Science
JF - Journal of Peptide Science
IS - 11
M1 - e3208
ER -