High pressure NMR reveals conformational perturbations by disease-causing mutations in amyloid β-peptide

Chem Commun (Camb). 2018 May 1;54(36):4609-4612. doi: 10.1039/c8cc01674g.

Abstract

Here we present the high pressure NMR characterization of Aβ42 and two Aβ40 variants with Alzheimer-causing mutations E22G and D23N. While chemical shifts only identified localized changes at ambient pressure compared with Aβ40, high pressure NMR revealed a common site with heightened pressure sensitivity at Q15, K16 and L17 in all three variants, which correlates to higher β-propensity at central hydrophobic cluster (CHC) and faster aggregation.

MeSH terms

  • Alzheimer Disease / genetics
  • Amyloid beta-Peptides / chemistry*
  • Amyloid beta-Peptides / genetics
  • Humans
  • Molecular Dynamics Simulation
  • Mutation
  • Nuclear Magnetic Resonance, Biomolecular / methods
  • Peptide Fragments / chemistry*
  • Peptide Fragments / genetics
  • Pressure
  • Protein Conformation, beta-Strand

Substances

  • Amyloid beta-Peptides
  • Peptide Fragments
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-42)