Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1993 Jul 1;90(13):5959–5963. doi: 10.1073/pnas.90.13.5959

A kinetic model for amyloid formation in the prion diseases: importance of seeding.

J H Come 1, P E Fraser 1, P T Lansbury Jr 1
PMCID: PMC46846  PMID: 8327467

Abstract

The transmissible spongiform encephalopathies (TSEs) are neurodegenerative diseases characterized by amyloid formation in the brain. The major amyloid protein is the prion protein (PrP). PrP and the beta-amyloid protein of Alzheimer disease share a similar sequence that, in both cases, may be responsible for the initiation of protein aggregation in vivo. We report here that a peptide based on this sequence in PrP (PrP96-111M) forms amyloid fibrils. The existence of a kinetic barrier to amyloid formation by this peptide was demonstrated, suggesting that formation of an ordered nucleus is the rate-determining step for aggregation. Seeding was demonstrated to occur with PrP96-111M amyloid fibrils but not with amyloid fibrils of a related peptide. This effect is consistent with the proposal that the aggregation of PrP, which characterizes TSE, involves a nucleation event analogous to the seeding of a crystallization.

Full text

PDF
5959

Images in this article

5960Fig. 2
on p.5960

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ASAKURA S., EGUCHI G., IINO T. RECONSTITUTION OF BACTERIAL FLAGELLA IN VITRO. J Mol Biol. 1964 Oct;10:42–56. doi: 10.1016/s0022-2836(64)80026-7. [DOI] [PubMed] [Google Scholar]
  2. Asakura S. A kinetic study of in vitro polymerization of flagellin. J Mol Biol. 1968 Jul 14;35(1):237–239. doi: 10.1016/s0022-2836(68)80051-8. [DOI] [PubMed] [Google Scholar]
  3. Baker H. E., Poulter M., Crow T. J., Frith C. D., Lofthouse R., Ridley R. M. Aminoacid polymorphism in human prion protein and age at death in inherited prion disease. Lancet. 1991 May 25;337(8752):1286–1286. doi: 10.1016/0140-6736(91)92953-y. [DOI] [PubMed] [Google Scholar]
  4. Beaven G. H., Gratzer W. B., Davies H. G. Formation and structure of gels and fibrils from glucagon. Eur J Biochem. 1969 Nov;11(1):37–42. doi: 10.1111/j.1432-1033.1969.tb00735.x. [DOI] [PubMed] [Google Scholar]
  5. Brown P., Goldfarb L. G., Gajdusek D. C. The new biology of spongiform encephalopathy: infectious amyloidoses with a genetic twist. Lancet. 1991 Apr 27;337(8748):1019–1022. doi: 10.1016/0140-6736(91)92670-w. [DOI] [PubMed] [Google Scholar]
  6. Caughey B. W., Dong A., Bhat K. S., Ernst D., Hayes S. F., Caughey W. S. Secondary structure analysis of the scrapie-associated protein PrP 27-30 in water by infrared spectroscopy. Biochemistry. 1991 Aug 6;30(31):7672–7680. doi: 10.1021/bi00245a003. [DOI] [PubMed] [Google Scholar]
  7. Caughey B., Race R. E. Potent inhibition of scrapie-associated PrP accumulation by congo red. J Neurochem. 1992 Aug;59(2):768–771. doi: 10.1111/j.1471-4159.1992.tb09437.x. [DOI] [PubMed] [Google Scholar]
  8. Caughey B., Raymond G. J. The scrapie-associated form of PrP is made from a cell surface precursor that is both protease- and phospholipase-sensitive. J Biol Chem. 1991 Sep 25;266(27):18217–18223. [PubMed] [Google Scholar]
  9. Chou P. Y., Fasman G. D. Prediction of protein conformation. Biochemistry. 1974 Jan 15;13(2):222–245. doi: 10.1021/bi00699a002. [DOI] [PubMed] [Google Scholar]
  10. Collinge J., Palmer M. S., Dryden A. J. Genetic predisposition to iatrogenic Creutzfeldt-Jakob disease. Lancet. 1991 Jun 15;337(8755):1441–1442. doi: 10.1016/0140-6736(91)93128-v. [DOI] [PubMed] [Google Scholar]
  11. Colon W., Kelly J. W. Partial denaturation of transthyretin is sufficient for amyloid fibril formation in vitro. Biochemistry. 1992 Sep 15;31(36):8654–8660. doi: 10.1021/bi00151a036. [DOI] [PubMed] [Google Scholar]
  12. DeArmond S. J., McKinley M. P., Barry R. A., Braunfeld M. B., McColloch J. R., Prusiner S. B. Identification of prion amyloid filaments in scrapie-infected brain. Cell. 1985 May;41(1):221–235. doi: 10.1016/0092-8674(85)90076-5. [DOI] [PubMed] [Google Scholar]
  13. Gabizon R., McKinley M. P., Groth D. F., Kenaga L., Prusiner S. B. Properties of scrapie prion protein liposomes. J Biol Chem. 1988 Apr 5;263(10):4950–4955. [PubMed] [Google Scholar]
  14. Gabizon R., McKinley M. P., Groth D., Prusiner S. B. Immunoaffinity purification and neutralization of scrapie prion infectivity. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6617–6621. doi: 10.1073/pnas.85.18.6617. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gasset M., Baldwin M. A., Lloyd D. H., Gabriel J. M., Holtzman D. M., Cohen F., Fletterick R., Prusiner S. B. Predicted alpha-helical regions of the prion protein when synthesized as peptides form amyloid. Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10940–10944. doi: 10.1073/pnas.89.22.10940. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Giaccone G., Verga L., Bugiani O., Frangione B., Serban D., Prusiner S. B., Farlow M. R., Ghetti B., Tagliavini F. Prion protein preamyloid and amyloid deposits in Gerstmann-Sträussler-Scheinker disease, Indiana kindred. Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9349–9353. doi: 10.1073/pnas.89.19.9349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Griffith J. S. Self-replication and scrapie. Nature. 1967 Sep 2;215(5105):1043–1044. doi: 10.1038/2151043a0. [DOI] [PubMed] [Google Scholar]
  18. Halverson K., Fraser P. E., Kirschner D. A., Lansbury P. T., Jr Molecular determinants of amyloid deposition in Alzheimer's disease: conformational studies of synthetic beta-protein fragments. Biochemistry. 1990 Mar 20;29(11):2639–2644. doi: 10.1021/bi00463a003. [DOI] [PubMed] [Google Scholar]
  19. Hofrichter J., Ross P. D., Eaton W. A. Kinetics and mechanism of deoxyhemoglobin S gelation: a new approach to understanding sickle cell disease. Proc Natl Acad Sci U S A. 1974 Dec;71(12):4864–4868. doi: 10.1073/pnas.71.12.4864. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hsiao K. K., Scott M., Foster D., Groth D. F., DeArmond S. J., Prusiner S. B. Spontaneous neurodegeneration in transgenic mice with mutant prion protein. Science. 1990 Dec 14;250(4987):1587–1590. doi: 10.1126/science.1980379. [DOI] [PubMed] [Google Scholar]
  21. Jarrett J. T., Lansbury P. T., Jr Amyloid fibril formation requires a chemically discriminating nucleation event: studies of an amyloidogenic sequence from the bacterial protein OsmB. Biochemistry. 1992 Dec 15;31(49):12345–12352. doi: 10.1021/bi00164a008. [DOI] [PubMed] [Google Scholar]
  22. Katzman R., Saitoh T. Advances in Alzheimer's disease. FASEB J. 1991 Mar 1;5(3):278–286. [PubMed] [Google Scholar]
  23. Lansbury P. T., Jr In pursuit of the molecular structure of amyloid plaque: new technology provides unexpected and critical information. Biochemistry. 1992 Aug 4;31(30):6865–6870. doi: 10.1021/bi00145a001. [DOI] [PubMed] [Google Scholar]
  24. Maggio J. E., Stimson E. R., Ghilardi J. R., Allen C. J., Dahl C. E., Whitcomb D. C., Vigna S. R., Vinters H. V., Labenski M. E., Mantyh P. W. Reversible in vitro growth of Alzheimer disease beta-amyloid plaques by deposition of labeled amyloid peptide. Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5462–5466. doi: 10.1073/pnas.89.12.5462. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Palmer M. S., Dryden A. J., Hughes J. T., Collinge J. Homozygous prion protein genotype predisposes to sporadic Creutzfeldt-Jakob disease. Nature. 1991 Jul 25;352(6333):340–342. doi: 10.1038/352340a0. [DOI] [PubMed] [Google Scholar]
  26. Prusiner S. B., Groth D. F., Bolton D. C., Kent S. B., Hood L. E. Purification and structural studies of a major scrapie prion protein. Cell. 1984 Aug;38(1):127–134. doi: 10.1016/0092-8674(84)90533-6. [DOI] [PubMed] [Google Scholar]
  27. Prusiner S. B., McKinley M. P., Bowman K. A., Bolton D. C., Bendheim P. E., Groth D. F., Glenner G. G. Scrapie prions aggregate to form amyloid-like birefringent rods. Cell. 1983 Dec;35(2 Pt 1):349–358. doi: 10.1016/0092-8674(83)90168-x. [DOI] [PubMed] [Google Scholar]
  28. Prusiner S. B. Molecular biology of prion diseases. Science. 1991 Jun 14;252(5012):1515–1522. doi: 10.1126/science.1675487. [DOI] [PubMed] [Google Scholar]
  29. Prusiner S. B., Scott M., Foster D., Pan K. M., Groth D., Mirenda C., Torchia M., Yang S. L., Serban D., Carlson G. A. Transgenetic studies implicate interactions between homologous PrP isoforms in scrapie prion replication. Cell. 1990 Nov 16;63(4):673–686. doi: 10.1016/0092-8674(90)90134-z. [DOI] [PubMed] [Google Scholar]
  30. Prusiner S. B. Scrapie prions. Annu Rev Microbiol. 1989;43:345–374. doi: 10.1146/annurev.mi.43.100189.002021. [DOI] [PubMed] [Google Scholar]
  31. Prusiner S. B. Some speculations about prions, amyloid, and Alzheimer's disease. N Engl J Med. 1984 Mar 8;310(10):661–663. doi: 10.1056/NEJM198403083101021. [DOI] [PubMed] [Google Scholar]
  32. Smith P. K., Krohn R. I., Hermanson G. T., Mallia A. K., Gartner F. H., Provenzano M. D., Fujimoto E. K., Goeke N. M., Olson B. J., Klenk D. C. Measurement of protein using bicinchoninic acid. Anal Biochem. 1985 Oct;150(1):76–85. doi: 10.1016/0003-2697(85)90442-7. [DOI] [PubMed] [Google Scholar]
  33. Spencer R. G., Halverson K. J., Auger M., McDermott A. E., Griffin R. G., Lansbury P. T., Jr An unusual peptide conformation may precipitate amyloid formation in Alzheimer's disease: application of solid-state NMR to the determination of protein secondary structure. Biochemistry. 1991 Oct 29;30(43):10382–10387. doi: 10.1021/bi00107a004. [DOI] [PubMed] [Google Scholar]
  34. Stahl N., Prusiner S. B. Prions and prion proteins. FASEB J. 1991 Oct;5(13):2799–2807. doi: 10.1096/fasebj.5.13.1916104. [DOI] [PubMed] [Google Scholar]
  35. Tagliavini F., Prelli F., Ghiso J., Bugiani O., Serban D., Prusiner S. B., Farlow M. R., Ghetti B., Frangione B. Amyloid protein of Gerstmann-Sträussler-Scheinker disease (Indiana kindred) is an 11 kd fragment of prion protein with an N-terminal glycine at codon 58. EMBO J. 1991 Mar;10(3):513–519. doi: 10.1002/j.1460-2075.1991.tb07977.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Weissmann C. A 'unified theory' of prion propagation. Nature. 1991 Aug 22;352(6337):679–683. doi: 10.1038/352679a0. [DOI] [PubMed] [Google Scholar]
  37. Weissmann C. Spongiform encephalopathies. The prion's progress. Nature. 1991 Feb 14;349(6310):569–571. doi: 10.1038/349569a0. [DOI] [PubMed] [Google Scholar]
  38. Xi Y. G., Ingrosso L., Ladogana A., Masullo C., Pocchiari M. Amphotericin B treatment dissociates in vivo replication of the scrapie agent from PrP accumulation. Nature. 1992 Apr 16;356(6370):598–601. doi: 10.1038/356598a0. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES