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

Biochemistry. 2017 Aug 15;56(32):4269-4278. doi: 10.1021/acs.biochem.7b00526. Epub 2017 Aug 1.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimicrobial Cationic Peptides / chemistry*
  • Humans
  • Nuclear Magnetic Resonance, Biomolecular*
  • Protein Structure, Secondary
  • Salivary Proteins and Peptides / chemistry*


  • Antimicrobial Cationic Peptides
  • BPIFA2 protein, human
  • Salivary Proteins and Peptides