Beschreibung:
<jats:title>Abstract</jats:title><jats:p>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 pGlu<jats:sub>3</jats:sub>-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 <jats:sup>13</jats:sup>C and <jats:sup>15</jats:sup>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 <jats:sup>13</jats:sup>C-<jats:sup>13</jats:sup>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.</jats:p>