Spectroscopic characterization of conformational differences between PrPC and PrPSc: an alpha-helix to beta-sheet transition.
Although no chemical modifications have been found to distinguish the cellular prion protein PrPC from its infectious analogue PrPSc, spectroscopic methods such as Fourier transform infrared (FTIR) spectroscopy reveal a major conformational difference. PrPC is rich in alpha-helix but is devoid of beta-sheet, whereas PrPSc is high in beta-sheet. N-terminal truncation of PrPSc by limited proteolysis does not destroy infectivity but it increases the beta-sheet content and shifts the FTIR absorption to lower frequencies, typical of the cross beta-pleated sheets of amyloids. Thus the formation of PrPSc from PrPC involves a conformational transition in which one or more alpha-helical regions of the protein is converted to beta-sheet. This transition is mimicked by synthetic peptides, allowing predictions of domains of PrP involved in prion diseases.
Baldwin
M A
MA
Department of Neurology, University of California, San Francisco 94143-0518.
Pan
K M
KM
Nguyen
J
J
Huang
Z
Z
Groth
D
D
Serban
A
A
Gasset
M
M
Mehlhorn
I
I
Fletterick
R J
RJ
Cohen
F E
FE
D000595:Amino Acid Sequence; D000818:Animals; D002942:Circular Dichroism; D006224:Cricetinae; D008969:Molecular Sequence Data; D018620:PrPSc Proteins; D011328:Prions / Q000737:chemistry* / Q000235:genetics; D011487:Protein Conformation; D011489:Protein Denaturation; D017433:Protein Structure, Secondary; D012608:Scrapie / Q000209:etiology; D017550:Spectroscopy, Fourier Transform Infrared
D018620:PrPSc Proteins; D011328:Prions