title: Fibrils of Truncated Pyroglutamyl-Modified Aβ Peptide Exhibit a Similar Structure as Wildtype Mature Aβ Fibrils.
abstract: Fibrillation of differently modified amyloid β peptides and deposition as senile plaques are hallmarks of Alzheimer's disease. N-terminally truncated variants, where the glutamate residue 3 is converted into cyclic pyroglutamate (pGlu), form particularly toxic aggregates. We compare the molecular structure and dynamics of fibrils grown from wildtype Aβ(1-40) and pGlu3-Aβ(3-40) on the single amino acid level. Thioflavin T fluorescence, electron microscopy, and X-ray diffraction reveal the general morphology of the amyloid fibrils. We found good agreement between the (13)C and (15)N NMR chemical shifts indicative for a similar secondary structure of both fibrils. A well-known interresidual contact between the two β-strands of the Aβ fibrils could be confirmed by the detection of interresidual cross peaks in a (13)C-(13)C NMR correlation spectrum between the side chains of Phe 19 and Leu 34. Small differences in the molecular dynamics of residues in the proximity to the pyroglutamyl-modified N-terminus were observed as measured by DIPSHIFT order parameter experiments.
authors.affiliation: Institute for Medical Physics and Biophysics, Leipzig University Härtelstr. 16-18, D-04107 Leipzig, Germany.
authors.forename: Holger A
authors.initials: HA
authors.lastname: Scheidt
authors.affiliation: Institute for Medical Physics and Biophysics, Leipzig University Härtelstr. 16-18, D-04107 Leipzig, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Adler
authors.affiliation: Institute of Anatomy, Leipzig University Eilenburger Str. 14-15, 04317 Leipzig, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Krueger
authors.affiliation: Institute for Medical Physics and Biophysics, Leipzig University Härtelstr. 16-18, D-04107 Leipzig, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Huster
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000648:ultrastructure; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000648:ultrastructure; D052160:Benzothiazoles; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D005453:Fluorescence; D011761:Pyrrolidonecarboxylic Acid / Q000737:chemistry*; D013844:Thiazoles / Q000737:chemistry
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D013844:Thiazoles; C009462:thioflavin T; D011761:Pyrrolidonecarboxylic Acid