Three-Dimensional Structure in Lipid Micelles of the Pediocin-like Antimicrobial Peptide Curvacin A

• Published in: Biochemistry (Easton) 2005-12, Vol.44 (49), p.16149-16157
• Main Authors: Haugen, Helen Sophie, Fimland, Gunnar, Nissen-Meyer, Jon, Kristiansen, Per Eugen
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Antimicrobial Cationic Peptides - chemistry; Antimicrobial Cationic Peptides - metabolism; Bacteriocins - chemistry; Bacteriocins - metabolism; Lactobacillus - chemistry; Lipids - chemistry; Micelles; Models, Molecular; Molecular Sequence Data; Protein Structure, Secondary; Protein Structure, Tertiary; Sequence Alignment
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi051215u

The 3D structure of the membrane-permeabilizing 41-mer pediocin-like antimicrobial peptide curvacin A produced by lactic acid bacteria has been studied by NMR spectroscopy. In DPC micelles, the cationic and hydrophilic N-terminal half of the peptide forms an S-shaped β-sheet-like domain stabilized by a disulfide bridge and a few hydrogen bonds. This domain is followed by two α-helices:  a hydrophilic 6-mer helix between residues 19 and 24 and an amphiphilic/hydrophobic 11-mer helix between residues 29 and 39. There are two hinges in the peptide, one at residues 16−18 between the N-terminal S-shaped β-sheet-like structure and the central 6-mer helix and one at residues 26−28 between the central helix and the 11-mer C-terminal helix. The latter helix is the only amphiphilic/hydrophobic part of the peptide and is thus presumably the part that penetrates into the hydrophobic phase of target-cell membranes. The hinge between the two helices may introduce the flexibility that allows the helix to dip into membranes. The helix−hinge−helix structure in the C-terminal half of curvacin A clearly distinguishes this peptide from the other pediocin-like peptides whose structures have been analyzed and suggests that curvacin A along with the structural homologues enterocin P and carnobacteriocin BM1 belong to a subgroup of the pediocin-like family of antimicrobial peptides.