Abeta(1-28) fragment of the amyloid peptide predominantly adopts a polyproline II conformation in an acidic solution

Biochemistry. 2004 Jun 8;43(22):6893-8. doi: 10.1021/bi049542+.

Abstract

To structurally characterize the nonaggregated state of the amyloid beta peptide, which assembles into the hallmark fibrils of Alzheimer disease, we investigated the conformation of the N-terminal extracellular peptide fragment Abeta(1-28) in D(2)O at acidic pD by utilizing combined FTIR and isotropic and anisotropic Raman spectra measured between 1550 and 1750 cm(-1). Peptide aggregation is avoided under the conditions chosen. The amide I' band was found to exhibit a significant noncoincidence effect in that the first moment of the anisotropic Raman and of the IR band profile appears red-shifted from that of the isotropic Raman scattering. A simulation based on a coupled oscillator model involving all 27 amide I' modes of the peptide reveals that the peptide adopts a predominantly polyproline II conformation. Our results are inconsistent with the notion that the monomeric form of Abeta(1-28) is a totally disordered, random-coil structure. Generally, they underscore the notion that polyproline II is a characteristic motif of the unfolded state of proteins and peptides.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acids / chemistry
  • Amyloid beta-Peptides / chemistry*
  • Humans
  • Peptide Fragments / chemistry*
  • Peptides / chemistry*
  • Protein Conformation*
  • Protein Folding
  • Spectroscopy, Fourier Transform Infrared
  • Spectrum Analysis, Raman

Substances

  • Acids
  • Amyloid beta-Peptides
  • Peptide Fragments
  • Peptides
  • amyloid beta-protein (1-28)
  • polyproline