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DOI: 10.5445/IR/1000075745

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

Zerweck, Jonathan; Strandberg, Erik; Kukharenko, Olga; Reichert, Johannes; Bürck, Jochen; Wadhwani, Parvesh; Ulrich, Anne S.

Abstract:
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 mo ... mehr


Zugehörige Institution(en) am KIT Institut für Biologische Grenzflächen (IBG)
Institut für Organische Chemie (IOC)
Publikationstyp Zeitschriftenaufsatz
Jahr 2017
Sprache Englisch
Identifikator ISSN: 2045-2322
URN: urn:nbn:de:swb:90-757459
KITopen ID: 1000075745
HGF-Programm 47.02.02; LK 01
Erschienen in Scientific reports
Band 7
Heft 1
Seiten 13153
Bemerkung zur Veröffentlichung Gefördert durch den KIT-Publikationsfonds
Schlagworte Antimicrobials; Membrane structure and assembly; Peptides; Solid-state NMR
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