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

12 Scopus citations

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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