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Role of the C-terminal fragment of human transthyretin in abnormal fibrillogenesis

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Abstract

Polypeptide chain fragments of recombinant transthyretin (TTR) with leucine-55 substituted by proline (L55P), which are involved in abnormal fibrillogenesis of this protein, were studied. No fibrils were produced in purified preparations of TTR(L55P) under the optimum conditions for fibrillogenesis but in absence of protease inhibitors. The ability of TTR for fibrillogenesis was lost because of a limited proteolysis resulting in detachment of the TTR polypeptide chain C-terminal fragment of ∼18 amino acid residues in length. This proteolysis seemed to occur with involvement of a bacterial serine endopeptidase sohB (EC 3.4.21), which was identified in TTR preparations by the MALDI-TOF method. The presence of the C-terminal fragment of the TTR polypeptide chain seems to be crucial for production of abnormal fibrils.

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Abbreviations

MALDI-TOF:

Matrix-Assisted Laser Desorption/Ionization-Time of Flight

ThT:

thioflavin T

TTR:

transthyretin

TTR(L55P):

transthyretin with leucine-55 substituted by proline

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Authors and Affiliations

  1. Department of Molecular Genetics, Institute of Experimental Medicine, Russian Academy of Medical Sciences, ul. Akademika Pavlova 12, 197376, St. Petersburg, Russia

    K. V. Solovyov, A. A. Gasteva, V. V. Egorov, T. D. Aleinikova, A. L. Shvartsman & M. M. Shavlovsky

  2. Institute of Influenza, Russian Academy of Medical Sciences, ul. Professora Popova 15/17, 196376, St. Petersburg, Russia

    A. K. Sirotkin

Authors
  1. K. V. Solovyov
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  2. A. A. Gasteva
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  3. V. V. Egorov
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  4. T. D. Aleinikova
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  5. A. K. Sirotkin
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  6. A. L. Shvartsman
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  7. M. M. Shavlovsky
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Correspondence to K. V. Solovyov.

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Original Russian Text © K. V. Solovyov, A. A. Gasteva, V. V. Egorov, T. D. Aleinikova, A. K. Sirotkin, A. L. Shvartsman, M. M. Shavlovsky, 2006, published in Biokhimiya, 2006, Vol. 71, No. 5, pp. 672–680.

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Solovyov, K.V., Gasteva, A.A., Egorov, V.V. et al. Role of the C-terminal fragment of human transthyretin in abnormal fibrillogenesis. Biochemistry (Moscow) 71, 543–549 (2006). https://doi.org/10.1134/S0006297906050129

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  • DOI: https://doi.org/10.1134/S0006297906050129

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