The structure, dynamics and orientation of antimicrobial peptides in membranes by multidimensional solid-state NMR spectroscopy.
Linear peptide antibiotics have been isolated from amphibians, insects and humans and used as templates to design cheaper and more potent analogues for medical applications. Peptides such as cecropins or magainins are < or = 40 amino acids in length. Many of them have been prepared by solid-phase peptide synthesis with isotopic labels incorporated at selected sites. Structural analysis by solid-state NMR spectroscopy and other biophysical techniques indicates that these peptide antibiotics strongly interact with lipid membranes. In bilayer environments they exhibit amphipathic alpha-helical conformations and alignments of the helix axis parallel to the membrane surface. This contrasts the transmembrane orientations observed for alamethicin or gramicidin A. Models that have been proposed to explain the antibiotic and pore-forming activities of membrane-associated peptides, as well as other experimental results, include transmembrane helical bundles, wormholes, carpets, detergent-like effects or the in-plane diffusion of peptide-induced bilayer instabilities.
Bechinger
B
B
Max Planck Institute for Biochemistry, Am Klopferspitz 18A, 82152, Martinsried, Germany. bechinge@biochem.mpg.de
D000408:Alamethicin / Q000737:chemistry; D000595:Amino Acid Sequence; D000663:Amphibians; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry*; D023181:Antimicrobial Cationic Peptides; D015195:Drug Design; D006096:Gramicidin / Q000737:chemistry; D007313:Insecta; D008051:Lipid Bilayers / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008555:Melitten / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship; D029867:Xenopus Proteins
D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D008051:Lipid Bilayers; D010455:Peptides; D029867:Xenopus Proteins; C053300:magainin 1 peptide, Xenopus; D006096:Gramicidin; D008555:Melitten; D000408:Alamethicin; C031161:cecropin A