Metal induced conformational changes of prion protein into Β-sheet isoforms similar to amyloid

Abstract

The transmissible spongiform encephalopathies (TSEs) are characterized by the conversion of the normal cellular prion protein to its abnormal pathogenic isoform which has an increased beta-sheet structure, an increased absorbance at the 700nm region and an enhanced capacity to form amyloids. Investigation on metal induced structural perturbation in selected prion protein peptide from hamster, mouse and humans had
residues of 23 – 231, 23 – 144, 23 – 106 and 90 – 231 in non-fibrilar versus amyloid isoforms analyzed with UV-visible scanning and Fourier transform infrared spectroscopy. The proteinase K resistant amyloid fragment (residues 90 – 231) exhibited a markedly high, broad absorbance at the 700nm region and an increase in beta-sheet character.
Addition of copper to the corresponding non-fibrillar 90 – 231 peptides also markedly increased the absorbance of this segment at the 700nm region, and led to an infrared shifted reflecting an increase in beta-sheet secondary structure similar to that of the amyloid. The copper-prompted increase in beta sheet structure and induced enhancement of the absorbance at the 70nm region when added to the monomeric
isoform similar to the amyloid suggest the importance of this structure in the determination of amyloid nucleation, stabilization, formation and perhaps prion infectivity.