Amyloid Fibril Formation by Polymerization of Abnormal Transthyretin

  • Shunsuke Migita
  • Hiroshi Nakashima


A hypothesis is presented in order to explain why single substitution of amino-acid in transthyretin induce familiar amyloidotic polyneuropathy (FAP). Single amino-acid substitution reported in FAP locate both end (C and D beta strands and the near) of transthyretin tetramer molecule. This means that original conformation of transthyretin does not affect so much by the single substitution. Originally the place concentrated amino-acid substitutions is hydrophilic region. Increase of the hydrophobicity or change of conformation at C and D strand region may induce a endless polymerization of abnormal tetramer and may make amyloid fibril. Amyloidogenesis need a long period of time, that means a weak tendency of polymerization will be sufficient with pathogenesis. Once polymerization will start, many non-covalent bindings between the large protein molecules proceed succesively, resulting insoluble amyloid.


Amyloid Fibril Beta Sheet Weak Tendency Single Substitution Tetramer Formation 
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  1. 1.
    Glenner, G.G., Eanes E.D., Balden H.A., et al: J. Histochem. Cytochem. 22;1141, 1974CrossRefGoogle Scholar
  2. 2.
    Kirschner D.A., Abraham C., Seikos D.J.: Proc. Natl. Acad. Sci. USA 83;503, 1986CrossRefGoogle Scholar
  3. 3.
    Gorevic P.D., Castano E.M., Sarma R., Frangione B.: Bioch. Biophys. Res. Commun. 147;854, 1987CrossRefGoogle Scholar
  4. 4.
    Tawara S., Nakazato M., Kangawa K., et al:Bioch. Biophys. Res. Commun. 116;860, 1983CrossRefGoogle Scholar
  5. 5.
    Benson M.D., Dwulet F.E.: Amyloidosis, ed. by G.G. Glenner, E.F. Osserman et al. p367, Plenum Press NY, 1986Google Scholar
  6. 6.
    Wallac M.D., Dwulet F.E., Connoally P.M., Benson M.D.: J. Clin. Invest. 78;6, 1986CrossRefGoogle Scholar
  7. 7.
    Pras M., Prelli F.E., Franklin E.C., et al.: Proc. Natl. Acad. Sci. USA 80;539, 1983CrossRefGoogle Scholar
  8. 8.
    Nakazato M., Tawara S., Kangawa K., et al.: Bioch. Biophys. Res. Commun. 123;921, 1984CrossRefGoogle Scholar
  9. 9.
    Benson M., Dwulet F.E.: Clin. Research 33; 590a, 1985Google Scholar
  10. 10.
    Kanda Y., Goodman D.S., Canfield R.E., et al.: J. Biol. Chem. 249;6795, 1974Google Scholar
  11. 11.
    Blake C.C.P., Geison M.J., Swan L.D.A.: J. Mol. Biol. 88;1, 1974CrossRefGoogle Scholar
  12. 12.
    Blake C.C.P., Geison M.J., Oatley S.J., et al.: J. Mol. Biol. 121;339, 1978CrossRefGoogle Scholar
  13. 13.
    Bernstein F.C., Koetzle T.F., Williams G.J.B., et al.: J. Mol. Biol. 112;535, 1977CrossRefGoogle Scholar
  14. 14.
    Wakasugi S., Maeda S., Shimada K., et al.: J. Biochem. 98;1707, 1985Google Scholar
  15. 15.
    Chau P.Y., Fasman G.D.: Biochemistry 13;222, 1974CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1988

Authors and Affiliations

  • Shunsuke Migita
    • 1
  • Hiroshi Nakashima
    • 1
    • 2
  1. 1.Department of Molecular Immunology, Cancer Research InstituteKanazawa UniversityJapan
  2. 2.School of Medical Profession, Kanazawa UniversityKanazawaJapan

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