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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
|
| pubmed:dateCreated |
1987-5-28
|
| pubmed:abstractText |
Prions cause scrapie and Creutzfeldt-Jakob disease (CJD); these infectious pathogens are composed largely, if not entirely, of protein molecules. No prion-specific polynucleotide has been identified. Purified preparations of scrapie prions contain high titers (greater than or equal to 10(9.5) ID50/ml), one protein (PrP 27-30) and amyloid rods (10-20 nm in diameter X 100-200 nm in length). Considerable evidence indicates that PrP 27-30 is required for and inseparable from scrapie infectivity. PrP 27-30 is encoded by a cellular gene and is derived from a larger protein, denoted PrPSc or PrP 33-35Sc, by protease digestion. A cellular isoform, designated PrPC or PrP 33-35C, is encoded by the same gene as PrPSc and both proteins appear to be translated from the same 2.1 kb mRNA. Monoclonal antibodies to PrP 27-30, as well as antisera to PrP synthetic peptides, specifically react with both PrPC and PrPSc, establishing their relatedness. PrPC is digested by proteinase K, while PrPSc is converted to PrP 27-30 under the same conditions. Prion proteins are synthesized with signal peptides and are integrated into membranes. Detergent extraction of microsomal membranes isolated from scrapie-infected hamster brains solubilizes PrPC but induces PrPSc to polymerize into amyloid rods. This procedure allows separation of the two prion protein isoforms and the demonstration that PrPSc accumulates during scrapie infection, while the level of PrPC does not change. The prion amyloid rods generated by detergent extraction are identical morphologically, except for length, to extracellular collections of prion amyloid filaments which form plaques in scrapie- and CJD-infected brains. The prion amyloid plaques stain with antibodies to PrP 27-30 and PrP peptides. PrP 33-35C does not accumulate in the extracellular space. Prion rods composed of PrP 27-30 can be dissociated into phospholipid vesicles with full retention of scrapie infectivity. The murine PrP gene (Prn-p) is linked to the Prn-i gene which controls the length of the scrapie incubation period. Prolonged incubation times are a cardinal feature of scrapie and CJD. While the central role of PrPSc in scrapie pathogenesis is well established, the chemical as well as conformational differences between PrPC and PrPSc are unknown but probably arise from post-translational modifications.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:issn |
0001-6322
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
72
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
299-314
|
| pubmed:dateRevised |
2008-11-21
|
| pubmed:meshHeading | |
| pubmed:year |
1987
|
| pubmed:articleTitle |
On the biology of prions.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Review,
Research Support, Non-U.S. Gov't
|