Transthyretin Acid Induced Denaturation is Required for Amyloid Fibril Formation in Vitro

  • Wilfredo Colon
  • Jeffery W. Kelly
Part of the Industry-University Cooperative Chemistry Program Symposia book series (IUCC)


The human plasma protein transthyretin (TTR), implicated as the causative agent in Familial Amyloid Polyneuropathy and Senile Systemic Amyloidosis, was transformed into amyloid fibrils in vitro under conditions that mimic the environment of a lysosome (pH 4.5). During the course of acid (HC1) induced denaturation, a folding intermediate associates to form amyloid fibrils. This procedure for making amyloid fibrils appears to be physiologically relevant and general in that IgG2 λ, another amyloidogenic protein which is associated with primary amyloidosis, was also transformed into amyloid fibrils at pH 4.5. This preliminary work suggests that denaturation is an integral part of the amyloid fibril formation mechanism in vivo.


Amyloid Fibril Familial Amyloid Polyneuropathy Amyloidogenic Protein Form Amyloid Fibril Primary Amyloidosis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    C. C. F. Blake, M. J. Geisow, I. D. A. Swan, C. Rerat, B. Rerat, J. Mol. Biol. 88, 1–12 (1974).PubMedCrossRefGoogle Scholar
  2. 2.
    C. C. F. Blake, M. J. Geisow, S. J. Oatley, J. Mol Biol. 121, 339–356 (1978).PubMedCrossRefGoogle Scholar
  3. 3.
    P. P. V. Jaarsveld, H. Edelhoch, D. S. Goodman, J. Robbins, J. Biol Chem. 248, 4698–4705 (1973).PubMedGoogle Scholar
  4. 4.
    S. F. Nilsson, L. Rask, P. A. Peterson, J. Biol Chem. 250, 8554–8563 (1975).PubMedGoogle Scholar
  5. 5.
    A. Raz, T. Shiratori, D. S. Goodman, J. Biol Chem. 245, 1903–1912 (1970).PubMedGoogle Scholar
  6. 6.
    D. S. Goodman, R. B. Leslie, Biochim. Biophys. Acta. 260, 670–678 (1972).PubMedCrossRefGoogle Scholar
  7. 7.
    H. Furuya, et al., Biochemistry 30, 2415–2421 (1991).PubMedCrossRefGoogle Scholar
  8. 8.
    M. D. Benson, TIBS 12, 88–92 (1989).Google Scholar
  9. 9.
    A. S. Cohen, E. Calkins, Nature 183, 1202–1203 (1959).PubMedCrossRefGoogle Scholar
  10. 10.
    E. M. Castano, B. Frangione, Laboratory Investigation 58, 122–132 (1988).PubMedGoogle Scholar
  11. 11.
    G. G. Glenner, et al., Science 174, 712–714 (1971).PubMedCrossRefGoogle Scholar
  12. 12.
    A. S. Cohen,, Laboratory Investigation 48, 1–4 (1983).PubMedGoogle Scholar
  13. 13.
    M. J. Burke, M. A. Roughvie, Biochemistry 11, (1972).Google Scholar
  14. 14.
    G. G. Glenner, E. D. Eanes, H. A. Bladen, R. P. Linke, J. D. Termine, J. Histochem. Cytochem. 22, 1141–1158 (1974).PubMedCrossRefGoogle Scholar
  15. 15.
    W. E. Klunk, J. W. Pettegrew, D. J. Abraham, The Journal of Histochem. and Cytochem. 37, 1273–81 (1989).CrossRefGoogle Scholar
  16. 16.
    H. Puchtler, F. Sweat, M. Levine, J. Histochem. Cytochem. 10, 355 (1962).CrossRefGoogle Scholar
  17. 17.
    G. G. Glenner, E. D. Eanes, D. L. Page, J. Biochem. Cytochem. 20, 821–826 (1972).CrossRefGoogle Scholar
  18. 18.
    R. D. Lillie Histopathological Technic and Practical Histochemistry pp 1-21. McGraw Hill NY (1976) 4th ed.Google Scholar
  19. 19.
    H. R. Allcock, F. W. Lampe, Contemporary Polymer Chemistry (Prentice-Hall, Englewood Cliffs, New Jersey, 1981).Google Scholar
  20. 20.
    C. Thomas, Sandritters’s Colr Atlas and Textbook of Histopathology (pp. 61) (Year Book Medical Publishers, Inc., Chicago, 1979).Google Scholar
  21. 21.
    R. A. Delellis, G. G. Glenner, J. Sri Ram, J. Histochem. and Cytochem. 16, 663–665 (1968).CrossRefGoogle Scholar
  22. 22.
    T. Shirahama, A. S. Cohen, Am J. Path. 81, 101 (1975).PubMedGoogle Scholar
  23. 23.
    L. I. Benowitz, e. al., Experimental Neurology 105, 237–250 (1989).CrossRefGoogle Scholar
  24. 24.
    Y. Goto, L. J. Calciano, A. L. Fink, Proc. Natl. Acad. Sci. 87, 573–577 (1990).PubMedCrossRefGoogle Scholar
  25. 25.
    Y. Goto, N. Takahashi, A. L. Fink, Biochemistry 29, 3480–88 (1990).PubMedCrossRefGoogle Scholar
  26. 26.
    Y. Goto, A. L. Fink, Biochemistry 28, 945–952 (1989).PubMedCrossRefGoogle Scholar
  27. 27.
    R. Jaenicke, Prog. Biophys. Molec. Biol. 49, 117–237 (1987).CrossRefGoogle Scholar
  28. 28.
    R. Jaenicke, R. Rudolph, in Methods in Enzymology C. H. W. Hirs, S. N. Timasheff, Eds. (Academic Press, New York, 1986), pp. 218–250.Google Scholar
  29. 29.
    G. Zettlmeissl, R. Rudolf, R. Jaenicke, Biochemistry 21, 3946–50 (1982).PubMedCrossRefGoogle Scholar
  30. 30.
    J. King, Bio/Technology 4, 297–303 (1986).CrossRefGoogle Scholar
  31. 31.
    R. Villafane, J. King, J. Mol. Biol. 204, 607–619 (1988).PubMedCrossRefGoogle Scholar
  32. 32.
    T. Pettersson, A. Carlstrom, H. Jornvall, Biochemistry 26, 4572–4583 (1987).PubMedCrossRefGoogle Scholar
  33. 33.
    T. Petterssom, A. Carlstrom, A. Ehrenberg, H. Jornvall, Biochem. Biophys. Res. Comm. 158, 341–347 (1989).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • Wilfredo Colon
    • 1
  • Jeffery W. Kelly
    • 1
  1. 1.Department of ChemistryTexas A&M UniversityCollege StationUSA

Personalised recommendations