Fibrils of Truncated Pyroglutamyl-Modified A? Peptide Exhibit a Similar Structure as Wildtype Mature A? Fibrils.

ABSTRACT: Fibrillation of differently modified amyloid ? 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 A?(1-40) and pGlu3-A?(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 ?-strands of the A? 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.

SUBMITTER: Scheidt HA 

PROVIDER: S-EPMC5030707 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature