Aβ amyloid fibrils possess a core structure highly resistant to hydrogen exchange

DOI Web Site 2 Citations
  • Indu Kheterpal
    Graduate School of Medicine, University of Tennessee Medical Center, Knoxville, TN 37920; and Department of Chemistry, University of Tennessee, Knoxville, TN 37996-1600
  • Shaolian Zhou
    Graduate School of Medicine, University of Tennessee Medical Center, Knoxville, TN 37920; and Department of Chemistry, University of Tennessee, Knoxville, TN 37996-1600
  • Kelsey D. Cook
    Graduate School of Medicine, University of Tennessee Medical Center, Knoxville, TN 37920; and Department of Chemistry, University of Tennessee, Knoxville, TN 37996-1600
  • Ronald Wetzel
    Graduate School of Medicine, University of Tennessee Medical Center, Knoxville, TN 37920; and Department of Chemistry, University of Tennessee, Knoxville, TN 37996-1600

Description

<jats:p>We describe here experiments designed to characterize the secondary structure of amyloid fibrils of the Alzheimer's amyloid plaque peptide Aβ, using hydrogen-deuterium exchange measurements evaluated by mass spectrometry. The results show that ≈50% of the amide protons of the polypeptide backbone of Aβ(1–40) resist exchange in aqueous, neutral pH buffer even after more than 1,000 h of incubation at room temperature. We attribute this extensive, strong protection to H-bonding by residues in core regions of β-sheet structure within the fibril. The backbone amide hydrogens exchange at variable rates, suggesting different degrees of protection within the fibril. These data suggest that it is unlikely that the entire Aβ sequence is involved in H-bonded secondary structure within the amyloid fibril. Future studies using the methods described here should reveal further details of Aβ fibril structure and assembly. These methods also should be amenable to studies of other amyloid fibrils and protein aggregates.</jats:p>

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