NR ACJO
AU Caughey,B.W.; Raymond,G.J.; Bessen,R.A.
TI Strain-dependent differences in beta-sheet conformations of abnormal prion protein
QU The Journal of Biological Chemistry 1998 Nov 27; 273(48): 32230-5
PT journal article
AB Strain diversity in the transmissible spongiform encephalopathies (TSEs) has been proposed to be determined by variations in the conformation of the abnormal, protease-resistant form of prion protein (PrPres). We have investigated whether infection of hamsters with three TSE strains resulted in the formation of PrPres with different conformations using limited proteinase K (PK) digestion and infrared spectroscopy. PrPres isolated from the brains of hamsters infected with the hyper (HY), drowsy (DY), and 263K TSE strains yielded similar SDS-polyacrylamide gel electrophoresis profiles prior to PK treatment. However, after limited digestion with PK, the PrPres from the DY strain exhibited a fragmentation pattern that was distinct from that of the other two strains. Infrared spectra of HY and 263K PrPres each had major absorption bands in the amide I region at 1626 and 1636 cm-1 both prior to and after digestion with PK. These bands were not evident in the DY PrPres spectra, which had a unique band at 1629-1630 cm-1 and stronger band intensity at both 1616 and 1694-1695 cm-1. Because absorbances from 1616 to 1636 cm-1 of protein infrared spectra are attributed primarily to beta-sheet structures, these findings indicate that the conformations of HY and 263K PrPres differ from DY PrPres at least in structural regions with beta-sheet secondary structure. These results support the hypothesis that strain-specific PrPres conformers can self-propagate by converting the normal prion protein to the abnormal conformers that induce phenotypically distinct TSE diseases.
MH Animal; Brain Chemistry; Hamsters; Prion Diseases; Prions/*chemistry/genetics; *Protein Conformation; *Protein Structure, Secondary; Species Specificity; Spectroscopy, Fourier Transform Infrared
AD Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, NIAID, National Institutes of Health, Hamilton, Montana 59840, USA. byron_caughey@nih.gov
SP englisch
PO USA