DOI: 10.1126/science.274.5295.2079. Evidence for the Conformation of the Pathologic Isoform of the Prion Protein Enciphering and Propagating Prion Diversity

Evidence for the Conformation of the Pathologic Isoform of the Prion Protein Enciphering and Propagating Prion Diversity

10.1126/science.274.5295.2079

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

The fundamental event in prion diseases seems to be a conformational change in cellular prion protein (PrP C ) whereby it is converted into the pathologic isoform PrP Sc . In fatal familial insomnia (FFI), the protease-resistant fragment of PrP Sc after deglycosylation has a size of 19 kilodaltons, whereas that from other inherited and sporadic prion diseases is 21 kilodaltons. Extracts from the brains of FFI patients transmitted disease to transgenic mice expressing a chimeric human-mouse PrP gene about 200 days after inoculation and induced formation of the 19-kilodalton PrP Sc fragment, whereas extracts from the brains of familial and sporadic Creutzfeldt-Jakob disease patients produced the 21-kilodalton PrP Sc fragment in these mice. The results presented indicate that the conformation of PrP Sc functions as a template in directing the formation of nascent PrP Sc and suggest a mechanism to explain strains of prions where diversity is encrypted in the conformation of PrP Sc .

Bibliography

Telling, G. C., Parchi, P., DeArmond, S. J., Cortelli, P., Montagna, P., Gabizon, R., Mastrianni, J., Lugaresi, E., Gambetti, P., & Prusiner, S. B. (1996). Evidence for the Conformation of the Pathologic Isoform of the Prion Protein Enciphering and Propagating Prion Diversity. Science, 274(5295), 2079â2082.

Authors 10

Glenn C. Telling (first)
Piero Parchi (additional)
Stephen J. DeArmond (additional)
Pietro Cortelli (additional)
Pasquale Montagna (additional)
Ruth Gabizon (additional)
James Mastrianni (additional)
Elio Lugaresi (additional)
Pierluigi Gambetti (additional)
Stanley B. Prusiner (additional)

References 53 Referenced 735

10.1126/science.142303
Prusiner S. B., ibid. 216, 136 (1982). / ibid. by Prusiner S. B. (1982)
___, ibid. 252, 1515 (1991). / ibid. (1991)
10.1073/pnas.90.23.10962
Prusiner S. B., et al., Cell 35, 349 (1983); (10.1016/0092-8674(83)90168-X) / Cell by Prusiner S. B. (1983)
Caughey B. W., et al., Biochemistry 30, 7672 (1991); (10.1021/bi00245a003) / Biochemistry by Caughey B. W. (1991)
Safar J., Roller P. P., Gajdusek D. C., Gibbs C. J., J. Biol. Chem. 268, 20276 (1993); (10.1016/S0021-9258(20)80725-X) / J. Biol. Chem. by Safar J. (1993)
Pergami P., Jaffe H., Safar J., Anal. Biochem. 236, 63 (1996). (10.1006/abio.1996.0132) / Anal. Biochem. by Pergami P. (1996)
Borchelt D. R., Scott M., Taraboulos A., Stahl N., Prusiner S. B., J. Cell Biol. 110, 743 (1990); (10.1083/jcb.110.3.743) / J. Cell Biol. by Borchelt D. R. (1990)
10.1021/bi00059a016
Meggendorfer F., Z. Gesmate. Neurol. Psychiatr. 128, 337 (1930); (10.1007/BF02864269) / Z. Gesmate. Neurol. Psychiatr. by Meggendorfer F. (1930)
Masters C. L., Gajdusek D. C., Gibbs C. J., Brain 104, 559 (1981). (10.1093/brain/104.3.559) / Brain by Masters C. L. (1981)
10.1038/338342a0
Poulter M., et al., Brain 115, 675 (1992); (10.1093/brain/115.3.675) / Brain by Poulter M. (1992)
Dlouhy S. R., et al., Nature Genet. 1, 64 (1992); (10.1038/ng0492-64) / Nature Genet. by Dlouhy S. R. (1992)
Petersen R. B., et al., Neurology 42, 1859 (1992); (10.1212/WNL.42.10.1859) / Neurology by Petersen R. B. (1992)
Gabizon R., et al., Am. J. Hum. Genet. 33, 828 (1993). / Am. J. Hum. Genet. by Gabizon R. (1993)
10.1038/382779a0
Chazot G., et al., Lancet 347, 1181 (1996); (10.1016/S0140-6736(96)90638-8) / Lancet by Chazot G. (1996)
Will R. G., et al., ibid., p. 921. / ibid. by Will R. G.
Telling G. C., et al., Proc. Natl. Acad. Sci. U.S.A. 91, 9936 (1994). (10.1073/pnas.91.21.9936) / Proc. Natl. Acad. Sci. U.S.A. by Telling G. C. (1994)
Telling G. C., et al., Cell 83, 79 (1995). (10.1016/0092-8674(95)90236-8) / Cell by Telling G. C. (1995)
Prusiner S. B., et al., ibid. 63, 673 (1990). / ibid. by Prusiner S. B. (1990)
10.1126/science.7909169
10.1056/NEJM199202133260704
10.1126/science.1439789
Petersen R. B., Parchi P., Richardson S. L., Urig C. B., Gambetti P., J. Biol. Chem. 271, 122661 (1996); / J. Biol. Chem. by Petersen R. B. (1996)
10.1038/382180a0
10.1038/376434a0
Collinge J., et al., Lancet 346, 569 (1995). (10.1016/S0140-6736(95)91405-6) / Lancet by Collinge J. (1995)
Parchi P., et al., Ann. Neurol. 38, 21 (1995). (10.1002/ana.410380107) / Ann. Neurol. by Parchi P. (1995)
Monari L., et al., Proc. Natl. Acad. Sci. U.S.A. 91, 2839 (1994); (10.1073/pnas.91.7.2839) / Proc. Natl. Acad. Sci. U.S.A. by Monari L. (1994)
Parchi P., et al., Ann. Neurol. 39, 767 (1996). (10.1002/ana.410390613) / Ann. Neurol. by Parchi P. (1996)
Telling G. Heye N. Prusiner S. B. unpublished data.
Taraboulos A., et al., Proc. Natl. Acad. Sci. U.S.A. 89, 7620 (1992). (10.1073/pnas.89.16.7620) / Proc. Natl. Acad. Sci. U.S.A. by Taraboulos A. (1992)
Manetto V., et al., Neurology 42, 312 (1992); (10.1212/WNL.42.2.312) / Neurology by Manetto V. (1992)
Gambetti P., Parchi P., Petersen R. B., Chen S. G., Lugaresi E., Brain Pathol. 5, 43 (1995). (10.1111/j.1750-3639.1995.tb00576.x) / Brain Pathol. by Gambetti P. (1995)
Hecker R., et al., Genes Dev. 6, 1213 (1992). (10.1101/gad.6.7.1213) / Genes Dev. by Hecker R. (1992)
DeArmond S. J. Telling G. C. Prusiner S. B. unpublished data.
Fraser H., Dickinson A. G., J. Comp. Pathol. 83, 29 (1973); (10.1016/0021-9975(73)90024-8) / J. Comp. Pathol. by Fraser H. (1973)
Bruce M. E., Dickinson A. G., Fraser H., Neuropathol. Appl. Neurobiol. 2, 471 (1976); (10.1111/j.1365-2990.1976.tb00521.x) / Neuropathol. Appl. Neurobiol. by Bruce M. E. (1976)
DeArmond S. J., et al., Proc. Natl. Acad. Sci. U.S.A. 90, 6449 (1993). (10.1073/pnas.90.14.6449) / Proc. Natl. Acad. Sci. U.S.A. by DeArmond S. J. (1993)
Dickinson A. G., Meikle V. M. H., Fraser H., J. Comp. Pathol. 78, 293 (1968); (10.1016/0021-9975(68)90005-4) / J. Comp. Pathol. by Dickinson A. G. (1968)
Bruce M. E., Dickinson A. G., J. Gen. Virol. 68, 79 (1987); (10.1099/0022-1317-68-1-79) / J. Gen. Virol. by Bruce M. E. (1987)
Kimberlin R. H., Walker C. A., Fraser H., ibid. 70, 2017 (1989); / ibid. by Kimberlin R. H. (1989)
Carp R. I., Callahan S. M., ibid. 72, 293 (1991). / ibid. by Carp R. I. (1991)
Scott M. DeArmond S. J. Prusiner S. B. unpublished data.
Bessen R. A., Marsh R. F., J. Gen. Virol. 73, 329 (1992); (10.1099/0022-1317-73-2-329) / J. Gen. Virol. by Bessen R. A. (1992)
10.1128/jvi.68.12.7859-7868.1994
10.1126/science.181.4096.223
10.1128/jvi.61.12.3688-3693.1987
Muramoto T., Kitamoto T., Tateishi J., Goto I., Am. J. Pathol. 140, 1411 (1992). / Am. J. Pathol. by Muramoto T. (1992)
Telling G. C., et al., Genes Dev. 10, 1736 (1996). (10.1101/gad.10.14.1736) / Genes Dev. by Telling G. C. (1996)

Dates

Type	When
Created	23 years, 1 month ago (July 27, 2002, 5:35 a.m.)
Deposited	1 year ago (Aug. 7, 2024, 7:47 a.m.)
Indexed	3 days, 3 hours ago (Aug. 29, 2025, 6:23 a.m.)
Issued	28 years, 8 months ago (Dec. 20, 1996)
Published	28 years, 8 months ago (Dec. 20, 1996)
Published Print	28 years, 8 months ago (Dec. 20, 1996)

Funders 0

None

BibTeX

@article{Telling_1996, title={Evidence for the Conformation of the Pathologic Isoform of the Prion Protein Enciphering and Propagating Prion Diversity}, volume={274}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.274.5295.2079}, DOI={10.1126/science.274.5295.2079}, number={5295}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Telling, Glenn C. and Parchi, Piero and DeArmond, Stephen J. and Cortelli, Pietro and Montagna, Pasquale and Gabizon, Ruth and Mastrianni, James and Lugaresi, Elio and Gambetti, Pierluigi and Prusiner, Stanley B.}, year={1996}, month=dec, pages={2079–2082} }

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