Solution and Solid-State Nuclear Magnetic Resonance Structural Investigations of the Antimicrobial Designer Peptide GL13K in Membranes

Nicole Harmouche, Christopher Aisenbrey, Fernando Porcelli, Youlin Xia, Sarah E Nelson, Xi Chen, Jesus Raya, Louic Vermeer, Conrado Aparicio, Gianluigi Veglia, Sven-Ulrik Gorr, Burkhard Bechinger

Research output: Contribution to journalArticle

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Abstract

The antimicrobial peptide GL13K encompasses 13 amino acid residues and has been designed and optimized from the salivary protein BPIFA2 to exhibit potent bacteriocidal and anti-biofilm activity against Gram-negative and Gram-positive bacteria as well as anti-lipopolysaccharide activity in vitro and in vivo. Here, the peptide was analyzed in a variety of membrane environments by circular dichroism spectroscopy and by high-resolution multidimensional solution nuclear magnetic resonance (NMR) spectroscopy. Whereas in the absence of membranes a random coil conformation predominates, the peptide adopts a helical structure from residue 5 to 11 in the presence of dodecylphosphocholine micelles. In contrast, a predominantly β-sheet structure was observed in the presence of lipid bilayers carrying negatively charged phospholipids. Whereas 15N solid-state NMR spectra are indicative of a partial alignment of the peptide 15N-1H vector along the membrane surface, 2H and 31P solid-state NMR spectra indicate that in this configuration the peptide exhibits pronounced disordering activities on the phospholipid membrane, which is possibly related to antimicrobial action. GL13K, thus, undergoes a number of conformational transitions, including a random coil state in solution, a helical structure upon dilution at the surface of zwitterionic membranes, and β-sheet conformations at high peptide:lipid ratios.

Original languageEnglish (US)
Pages (from-to)4269-4278
Number of pages10
JournalBiochemistry
Volume56
Issue number32
DOIs
StatePublished - Aug 15 2017

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Magnetic Resonance Spectroscopy
Nuclear magnetic resonance
Membranes
Peptides
Conformations
Phospholipids
Salivary Proteins and Peptides
Circular dichroism spectroscopy
Lipid bilayers
Biofilms
Lipid Bilayers
Gram-Positive Bacteria
Micelles
Circular Dichroism
Nuclear magnetic resonance spectroscopy
Dilution
Lipopolysaccharides
Spectrum Analysis
Bacteria
Lipids

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Solution and Solid-State Nuclear Magnetic Resonance Structural Investigations of the Antimicrobial Designer Peptide GL13K in Membranes. / Harmouche, Nicole; Aisenbrey, Christopher; Porcelli, Fernando; Xia, Youlin; Nelson, Sarah E; Chen, Xi; Raya, Jesus; Vermeer, Louic; Aparicio, Conrado; Veglia, Gianluigi; Gorr, Sven-Ulrik; Bechinger, Burkhard.

In: Biochemistry, Vol. 56, No. 32, 15.08.2017, p. 4269-4278.

Research output: Contribution to journalArticle

Harmouche, Nicole ; Aisenbrey, Christopher ; Porcelli, Fernando ; Xia, Youlin ; Nelson, Sarah E ; Chen, Xi ; Raya, Jesus ; Vermeer, Louic ; Aparicio, Conrado ; Veglia, Gianluigi ; Gorr, Sven-Ulrik ; Bechinger, Burkhard. / Solution and Solid-State Nuclear Magnetic Resonance Structural Investigations of the Antimicrobial Designer Peptide GL13K in Membranes. In: Biochemistry. 2017 ; Vol. 56, No. 32. pp. 4269-4278.
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