New Concepts for the Mechanisms of Action of Antimicrobial Peptides from Solid-state NMR Investigations

Abstract

The development and application of solid-state NMR techniques during the investigation of the functional mechanisms of membrane-active peptides is presented with a focus on the antimicrobial sequences magainin 2, PGLa and designed derivatives. Important insights have been obtained from MAS and oriented solid-state NMR approaches. In the latter case the peptides are reconstituted into supported lipid bilayers and aligned with the membrane normal parallel to the magnetic field direction. This approach provides information about the structure, topology and dynamics of the peptide, as well as the orientational and conformational order of the lipids. A strong dependence of the interaction modes was observed on both the lipid head group and fatty acyl chain composition, which underlines the importance of a careful choice of experimental conditions. Together, solid-state NMR of peptides and lipids provides a comprehensive view of the peptide–lipid interactions, which has resulted in conceptionally new models for their antimicrobial action and the synergistic enhancement observed for combinations of magainin 2 and PGLa. Furthermore, a detailed analysis of the membrane topology of the antimicrobial designer peptide LAH4 reconstituted into supported lipid bilayers at pH 5.3 is presented illustrating the protocol and its limitations.