title: Study of the conformational transition of A beta(1-42) using D-amino acid replacement analogues.
abstract: A critical event in Alzheimer's disease is the transition of Abeta peptides from their soluble forms into disease-associated beta-sheet-rich conformers. Structural analysis of a complete D-amino acid replacement set of Abeta(1-42) enabled us to localize in the full-length 42-mer peptide the region responsible for the conformational switch into a beta-sheet structure. Although NMR spectroscopy of trifluoroethanol-stabilized monomeric Abeta(1-42) delineated two separated helical domains, only the destabilization of helix I, comprising residues 11-24, caused a transition to a beta-sheet structure. This conformational alpha-to-beta switch was directly accompanied by an aggregation process leading to the formation of amyloid fibrils.
authors.affiliation: Institute of Molecular Pharmacology and Max Delbrück Center of Molecular Medicine, Berlin, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Janek
authors.forename: S
authors.initials: S
authors.lastname: Rothemund
authors.forename: K
authors.initials: K
authors.lastname: Gast
authors.forename: M
authors.initials: M
authors.lastname: Beyermann
authors.forename: J
authors.initials: J
authors.lastname: Zipper
authors.forename: H
authors.initials: H
authors.lastname: Fabian
authors.forename: M
authors.initials: M
authors.lastname: Bienert
authors.forename: E
authors.initials: E
authors.lastname: Krause
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000596:Amino Acids / Q000138:chemical synthesis* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000138:chemical synthesis* / Q000378:metabolism* / Q000648:ultrastructure; D002942:Circular Dichroism; D006801:Humans; D008027:Light; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000378:metabolism* / Q000648:ultrastructure; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012542:Scattering, Radiation; D012997:Solvents; D017550:Spectroscopy, Fourier Transform Infrared; D013816:Thermodynamics; D014270:Trifluoroethanol
chemical_list: D000596:Amino Acids; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D012997:Solvents; C075222:amyloid beta-protein (1-42); D014270:Trifluoroethanol