title: Self-assembly of flexible β-strands into immobile amyloid-like β-sheets in membranes as revealed by solid-state 19F NMR.
abstract: The cationic peptide [KIGAKI](3) was designed as an amphiphilic β-strand and serves as a model for β-sheet aggregation in membranes. Here, we have characterized its molecular conformation, membrane alignment, and dynamic behavior using solid-state (19)F NMR. A detailed structure analysis of selectively (19)F-labeled peptides was carried out in oriented DMPC bilayers. It showed a concentration-dependent transition from monomeric β-strands to oligomeric β-sheets. In both states, the rigid (19)F-labeled side chains project straight into the lipid bilayer but they experience very different mobilities. At low peptide-to-lipid ratios ≤1:400, monomeric [KIGAKI](3) swims around freely on the membrane surface and undergoes considerable motional averaging, with essentially uncoupled φ/ψ torsion angles. The flexibility of the peptide backbone in this 2D plane is reminiscent of intrinsically unstructured proteins in 3D. At high concentrations, [KIGAKI](3) self-assembles into immobilized β-sheets, which are untwisted and lie flat on the membrane surface as amyloid-like fibrils. This is the first time the transition of monomeric β-strands into oligomeric β-sheets has been characterized by solid-state NMR in lipid bilayers. It promises to be a valuable approach for studying membrane-induced amyloid formation of many other, clinically relevant peptide systems.
authors.affiliation: Karlsruhe Institute of Technology (KIT), Institute of Biological Interfaces (IBG-2), POB 3640, D-76021 Karlsruhe, Germany.
authors.forename: Parvesh
authors.initials: P
authors.lastname: Wadhwani
authors.forename: Erik
authors.initials: E
authors.lastname: Strandberg
authors.forename: Nico
authors.initials: N
authors.lastname: Heidenreich
authors.forename: Jochen
authors.initials: J
authors.lastname: Bürck
authors.forename: Susanne
authors.initials: S
authors.lastname: Fanghänel
authors.forename: Anne S
authors.initials: AS
authors.lastname: Ulrich
mesh_terms: D000682:Amyloid / Q000737:chemistry*; D005462:Fluorine Radioisotopes / Q000737:chemistry; D008051:Lipid Bilayers; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D017433:Protein Structure, Secondary
chemical_list: D000682:Amyloid; D005462:Fluorine Radioisotopes; D008051:Lipid Bilayers