Fibrils of Truncated Pyroglutamyl-Modified A[beta] Peptide Exhibit a Similar Structure as Wildtype Mature A[beta] Fibrils

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.