title: A stereochemical switch in the aDrs model system, a candidate for a functional amyloid.
abstract: Amyloid fibrils are commonly observed to adopt multiple distinct morphologies, which eventually can have significantly different neurotoxicities, as e.g. demonstrated in case of the Alzheimer peptide. The architecture of amyloid deposits is apparently also determined by the stereochemistry of amino acids. Post-translational changes of the chirality of certain residues may thus be a factor in controlling the formation of functional or disease-related amyloids. Anionic dermaseptin (aDrs), an unusual peptide from the skin secretions of the frog Pachymedusa dacnicolor, assembles to amyloid-like fibrils in a pH-dependent manner, which could play a functional role in defense. aDrs can be enzymatically converted into the diastereomer [d-Leu2]-aDrs by an l/d-isomerase. EM and AFM on fibrils formed by these isomers have shown that their predominant morphology is controlled by the stereochemistry of residue 2, whereas kinetic and thermodynamic parameters of aggregation are barely affected. When fibrils were grown from preformed seeds, backbone stereochemistry rather than templating-effects apparently dominated the superstructural organization of the isomers. Interestingly, MD indicated small differences in the conformational propensities between the isomers. Our results demonstrate how d-amino acid substitutions could take active part in the formation of functional or disease-related amyloid. Moreover, these findings contribute to the development of amyloid-based nanomaterials.
authors.affiliation: Institute of Organic Chemistry, CSNA Center for Surface- and Nanoanalytics, Johannes Kepler University Linz, Austria.
authors.forename: Ruth
authors.initials: R
authors.lastname: Gößler-Schöfberger
authors.forename: Günter
authors.initials: G
authors.lastname: Hesser
authors.forename: Maria M
authors.initials: MM
authors.lastname: Reif
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Friedmann
authors.forename: Bernadette
authors.initials: B
authors.lastname: Duscher
authors.forename: José Luis
authors.initials: JL
authors.lastname: Toca-Herrera
authors.forename: Chris
authors.initials: C
authors.lastname: Oostenbrink
authors.forename: Alexander
authors.initials: A
authors.lastname: Jilek
mesh_terms: D029845:Amphibian Proteins / Q000737:chemistry / Q000502:physiology*; D000682:Amyloid / Q000737:chemistry / Q000502:physiology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000502:physiology*; D007700:Kinetics; D018625:Microscopy, Atomic Force; D046529:Microscopy, Electron, Transmission; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D017550:Spectroscopy, Fourier Transform Infrared; D013237:Stereoisomerism; D013816:Thermodynamics
chemical_list: D029845:Amphibian Proteins; D000682:Amyloid; D023181:Antimicrobial Cationic Peptides; C070905:dermaseptin