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

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.