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| STRUCTURAL STUDIES OF THE SCRAPIE PRION PROTEIN USING MASS-SPECTROMETRY AND AMINO-ACID SEQUENCING |
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| Author(s): STAHL N, BALDWIN MA, TEPLOW DB, HOOD L, GIBSON BW, BURLINGAME AL, PRUSINER SB |
| Source: BIOCHEMISTRY Volume: 32 Issue: 8 Pages: 1991-2002 Published: MAR 2 1993 |
| Times Cited: 398 References: 104 |
| Abstract: The only component of the infectious scrapie prion identified to date is a protein designated PrP(Sc). A posttranslational process converts the cellular PrP isoform (PrP(C)) into PrP(Sc). Denatured PrP(Sc) was digested with endoproteases, and the resulting fragments were isolated by HPLC. By both mass spectrometry and Edman sequencing, the primary structure of PrP(Sc) was found to be the same as that deduced from the PrP gene sequence, arguing that neither RNA editing nor protein splicing feature in the synthesis of PrP(Sc). Mass spectrometry also was used to search for posttranslational chemical modifications other than the glycosylinositol phospholipid anchor attached to the C-terminus and two Asn-linked oligosaccharides already known to occur on both PrP(Sc) and PrP(C). These results contend that PrP(Sc) molecules do not differ from PrP(C) at the level of an amino acid substitution or a posttranslational chemical modification; however, we cannot eliminate the possibility that a small fraction of PrP(Sc) is modified by an as yet unidentified posttranslational process or that PrP(C) carries a modification that is removed in the formation of PrP(Sc). It seems likely that PrP(Sc) differs from PrP(C) in its secondary and tertiary structure, but the possibility of a tightly bound, disease-specific molecule which purifies with PrP(Sc) must also be considered. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV CALIF SAN FRANCISCO, DEPT NEUROL, HSE-781, SAN FRANCISCO, CA 94143 USA
2. UNIV CALIF SAN FRANCISCO, DEPT PHARMACEUT CHEM, SAN FRANCISCO, CA 94143 USA
3. UNIV CALIF SAN FRANCISCO, DEPT BIOCHEM & BIOPHYS, SAN FRANCISCO, CA 94143 USA
4. CALTECH, DIV BIOL, PASADENA, CA 91125 USA |
| Publisher: AMER CHEMICAL SOC, 1155 16TH ST, NW, WASHINGTON, DC 20036 |
| Subject Category: Biochemistry & Molecular Biology |
| IDS Number: KP582 |
| ISSN: 0006-2960 |
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