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Molecular mechanism of synergy between the antimicrobial peptides PGLa and magainin 2

Zerweck, Jonathan 1; Strandberg, Erik 2; Kukharenko, Olga 1; Reichert, Johannes 2; Bürck, Jochen 2; Wadhwani, Parvesh 2; Ulrich, Anne S. 1,2
1 Institut für Organische Chemie (IOC), Karlsruher Institut für Technologie (KIT)
2 Institut für Biologische Grenzflächen (IBG), Karlsruher Institut für Technologie (KIT)


PGLa and magainin 2 (MAG2) are amphiphilic α-helical membranolytic peptides from frog skin with known synergistic antimicrobial activity. By systematically mutating residues in the two peptides it was possible to identify the ones crucial for the synergy, as monitored by biological assays, fluorescence vesicle leakage, and solid-state 15N-NMR. Electrostatic interactions between anionic groups in MAG2 and cationic residues in PGLa enhance synergy but are not necessary for the synergistic effect. Instead, two Gly residues (7 and 11) in a so-called GxxxG motif in PGLa are necessary for synergy. Replacing either of them with Ala or another hydrophobic residue completely abolishes synergy according to all three methods used. The designer-made peptide MSI-103, which has a similar sequence as PGLa, shows no synergy with MAG2, but by introducing two Gly mutations it was possible to make it synergistic. A molecular model is proposed for the functionally active PGLa-MAG2 complex, consisting of a membrane-spanning antiparallel PGLa dimer that is stabilized by intimate Gly-Gly contacts, and where each PGLa monomer is in contact with one MAG2 molecule at its C-terminus.

Volltext §
DOI: 10.5445/IR/1000075745
DOI: 10.1038/s41598-017-12599-7
Zitationen: 73
Web of Science
Zitationen: 70
Zitationen: 86
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Biologische Grenzflächen (IBG)
Institut für Organische Chemie (IOC)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2017
Sprache Englisch
Identifikator ISSN: 2045-2322
KITopen-ID: 1000075745
HGF-Programm 47.02.02 (POF III, LK 01) Zellpopul.auf Biofunk.Oberflächen IBG-2
Erschienen in Scientific reports
Verlag Nature Research
Band 7
Seiten Art.Nr. 13153
Bemerkung zur Veröffentlichung Gefördert durch den KIT-Publikationsfonds
Vorab online veröffentlicht am 13.10.2017
Schlagwörter Antimicrobials; Membrane structure and assembly; Peptides; Solid-state NMR
Nachgewiesen in Dimensions
Web of Science
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