The membrane interactions of antimicrobial peptides revealed by solid-state NMR spectroscopy

• Published in: Chemistry and physics of lipids 2012-04, Vol.165 (3), p.282-301
• Main Authors: Bechinger, Burkhard, Salnikov, Evgeniy S.
• Format: Article
• Language: English
• Subjects: alamethicin; Amino Acid Sequence; anti-infective agents; anti-infective properties; Antimicrobial Cationic Peptides - chemistry; Antimicrobial Cationic Peptides - metabolism; antimicrobial peptides; Cell Membrane - chemistry; Cell Membrane - metabolism; deuterium; Distinctin; Humans; hydrophobicity; Lipid Bilayers - chemistry; Lipid Bilayers - metabolism; Magainin; Magnetic Resonance Spectroscopy - methods; mechanism of action; Membrane topology; Molecular Sequence Data; Molecular shape concept; Movement; nuclear magnetic resonance spectroscopy; Peptide–lipid interactions; phospholipids; polypeptides; Protein Multimerization; stable isotopes; Synergism; topology
• ISSN: 0009-3084; 1873-2941
• DOI: 10.1016/j.chemphyslip.2012.01.009

► Solid-state NMR allows investigations of the structure and topology of membrane-associated antimicrobial peptides in great detail in liquid disordered bilayers. ► Modulations of the thickness and macroscopic phase of membranes by AMPs are revealed by solid-state NMR. ► 2H and 31P NMR spectra correlate with lipid morphology. ► Lipid-mediated peptide–peptide interactions and topologies have been observed. ► Investigations of dimers and synergisms reveals new mechanistic details. Solid-state NMR spectroscopic techniques provide valuable information about the structure, dynamics and topology of membrane-inserted polypeptides. In particular antimicrobial peptides (or ‘host defence peptides’) have early on been investigated by solid-state NMR spectroscopy and many technical innovations in this domain have been developed with the help of these compounds when reconstituted into oriented phospholipid bilayers. Using solid-state NMR spectroscopy it could be shown for the first time that magainins or derivatives thereof exhibit potent antimicrobial activities when their cationic amphipathic helix is oriented parallel to the bilayer surface, a configuration found in later years for many other linear cationic amphipathic peptides. In contrast transmembrane alignments or lipid-dependent tilt angles have been found for more hydrophobic sequences such as alamethicin or β-hairpin antimicrobials. This review presents various solid-state NMR approaches and develops the basic underlying concept how angular information can be obtained from oriented samples. It is demonstrated how this information is used to calculate structures and topologies of peptides in their native liquid-disordered phospholipid bilayer environment. Special emphasis is given to discuss which NMR parameters provide the most complementary information, the minimal number of restraints needed and the effect of motions on the analysis of the NMR spectra. Furthermore, recent 31P and 2H solid-state NMR measurements of lipids are presented including some unpublished data which aim at investigating the morphological and structural changes of oriented or non-oriented phospholipids. Finally the structural models that have been proposed for the mechanisms of action of these peptides will be presented and discussed in view of the solid-state NMR and other biophysical experiments.