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Prions and prion proteins 1
Author(s) -
Stahl Neil,
Prusiner Stanley B.
Publication year - 1991
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.5.13.1916104
Subject(s) - scrapie , amino acid , peptide sequence , nucleic acid , chemistry , biochemistry , glycoprotein , complementary dna , bovine spongiform encephalopathy , sialic acid , biology , prion protein , gene , medicine , disease , pathology
Neurodegenerative diseases of animals and humans including scrapie, bovine spongiform encephalopathy, and Creutzfeldt‐Jakob disease are caused by unusual infectious pathogens called prions. There is no evidence for a nucleic acid in the prion, but diverse experimental results indicate that a host‐derived protein called PrP Sc is a component of the infectious particle. Experiments with scrapie‐infected cultured cells show that PrP Sc is derived from a normal cellular protein called PrP C through an unknown posttranslational process. We have analyzed the amino acid sequence and posttranslational modifications of PrP Sc and its proteolytically truncated core PrP 27‐30 to identify potential candidate modifications that could distinguish PrP Sc from PrP C . The amino acid sequence of PrP 27‐30 corresponds to that predicted from the gene and cDNA. Mass spectrometry of peptides derived from PrP Sc has revealed numerous modifications including two N‐linked carbohydrate moieties, removal of an amino‐terminal signal sequence, and alternative COOH termini. Most molecules contain a glycosylinositol phospholipid (GPI) attached at Ser‐231 that results in removal of 23 amino acids from the COOH terminus, whereas 15% of the protein molecules are truncated to end at Gly‐228. The structure of the GPI from PrP Sc has been analyzed and found to be novel, including the presence of sialic acid. Other experiments suggest that the N‐linked oligosaccharides are not necessary for PrP Sc formation. Although detailed comparison of PrP Sc with PrP C is required, there is no obvious way in which any of the modifications might confer upon prp Sc its unusual physical properties and allow it to act as a component of the prion. If no chemical difference is found between PrP C and PrP Sc , then the two isoforms of the prion protein may differ only in their conformations or by the presence of bound cellular components.—Stahl, N.; Prusiner, S. B. Prions and prion proteins. FASEB J. 5: 2799‐2807; 1991.