Abstract
The amphipathic α-helical antimicrobial peptide MSI-103 (aka KIA21) can form stable transmembrane pores when the bilayer takes on a positive spontaneous curvature, e.g. by the addition of lyso-lipids. Solid-state 31P- and 15N-NMR demonstrated an enrichment of lyso-lipids in these toroidal wormholes. Anionic lyso-lipids provided additional stabilization by electrostatic interactions with the cationic peptides. The remaining lipid matrix did not affect the nature of the pore, as peptides maintained the same orientation independent of lipid charge, and a change in membrane thickness did not considerably affect their tilt angle. Under optimized conditions (i.e. in the presence of lyso-lipids and appropriate bilayer thickness), stable and well-aligned pores could be obtained for solid-state 2H-NMR analysis. These data revealed for the first time the complete 3D alignment of this representative amphiphilic peptide in fluid membranes, which is compatible with either monomeric helices as constituents, or left-handed supercoiled dimers as building blocks from which the overall toroidal wormhole is assembled.
Highlights
The amphipathic α-helical antimicrobial peptide MSI-103 can form stable transmembrane pores when the bilayer takes on a positive spontaneous curvature, e.g. by the addition of lyso-lipids
We used solid-state 31P, 15N, and 2H-NMR to characterize the orientation of MSI-103 in membranes containing lyso-lipids, which have been recently demonstrated to support the formation of stable pores
We had studied the orientation of MSI-103 in many other lipid systems using 2Hand 19F-NMR16,19, where the orientation was found to be dominated by the spontaneous curvature of the lipids
Summary
The amphipathic α-helical antimicrobial peptide MSI-103 (aka KIA21) can form stable transmembrane pores when the bilayer takes on a positive spontaneous curvature, e.g. by the addition of lyso-lipids. Under optimized conditions (i.e. in the presence of lyso-lipids and appropriate bilayer thickness), stable and well-aligned pores could be obtained for solid-state 2H-NMR analysis These data revealed for the first time the complete 3D alignment of this representative amphiphilic peptide in fluid membranes, which is compatible with either monomeric helices as constituents, or lefthanded supercoiled dimers as building blocks from which the overall toroidal wormhole is assembled. C crystalline state – all peptides lie flat on the membrane surface in bilayers made of lipids containing unsaturated acyl chains, such as POPC and POPG18 They were found to be inserted in a transmembrane orientation in lipid systems with a highly positive spontaneous curvature, such as DMPC and lyso-MPC18. These trapped pores can be characterized in detail by solid-state 2H-NMR, under conditions that presumably reflect the instantaneous moment of transient pore formation
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