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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Prusiner, S. B. Rogers, M. Yehiely, F. Scott, M. |
| Description | Author Affiliation: Rogers M ( Department of Neurology, University of California, San Francisco 94143.); |
| Abstract | The only known component of the infectious prion is a posttranslationally modified protein known as the scrapie isoform of the prion protein, PrPSc. Upon limited proteolysis, a protease-resistant fragment designated PrP 27-30 is formed. Using in vitro mutagenesis, we examined the role of the N and C termini in the formation of PrPSc in persistently infected, mouse neuroblastoma (ScN2a) cells. Neither deletion of amino acids 23-88, which are also removed by proteinase K in the formation of PrP 27-30, nor deletion of the five octapeptide repeats within this region altered synthesis of PrPSc. Elongation of PrP with one, two, four, or six octapeptide repeats in addition to the five found in wild-type PrP did not alter the synthesis of PrPSc. Truncation of the C terminus was accomplished by substituting a translation stop codon for the predicted glycosylinositol phospholipid (GPI) anchor-attachment signal corresponding to amino acids 231-254. Expression of this C-terminal PrP mutant in ScN2a cells produced PrPSc that appeared to lack a GPI anchor. We conclude that neither the GPI anchor nor the N-terminal 66 amino acids are required for the synthesis of PrPSc as measured by the acquisition of limited resistance to proteinase K digestion. Whether these truncated or elongated PrP molecules are competent to participate in the formation of infectious prions remains to be established. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 8 |
| Volume Number | 90 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 1993-05-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Genes, Viral Prions Genetics Metabolism Amino Acid Sequence Animals Chimera Cricetinae Glycosylphosphatidylinositols Mesocricetus Mice Molecular Sequence Data Neuroblastoma Oligodeoxyribonucleotides Isolation & Purification Recombination, Genetic Repetitive Sequences, Nucleic Acid Restriction Mapping Tumor Cells, Cultured Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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