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Instability, unfolding and aggregation of human lysozyme variants underlying amyloid fibrillogenesis

Nature volume 385, pages 787–793 (1997)Cite this article

Abstract

Tissue deposition of soluble proteins as amyloid fibrils underlies a range of fatal diseases. The two naturally occurring human lysozyme variants are both amyloidogenic, and are shown here to be unstable. They aggregate to form amyloid fibrils with transformation of the mainly helical native fold, observed in crystal structures, to the amyloid fibril cross-β fold. Biophysical studies suggest that partly folded intermediates are involved in fibrillogenesis, and this may be relevant to amyloidosis generally.

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Author notes

  1. Vittorio Bellotti

    Present address: Dipartimento di Biochimica, Università di Pavia, Via Taramelli 3B, 27100, Pavia, Italy

  2. Sheena E. Radford

    Present address: Department of Biochemistry and Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK

  3. David R. Booth and Margaret Sunde: These authors contributed equally to this work.

Authors and Affiliations

  1. Immunological Medicine Unit, Royal Postgraduate Medical School, Hammersmith Hospital, London, W12 0NN, UK

    David R. Booth, Vittorio Bellotti, Winston L. Hutchinson, Philip N. Hawkins & Mark B. Pepys

  2. Laboratory of Molecular Biophysics, Oxford Centre for Molecular Sciences, University of Oxford, Oxford, OX1 3QT, UK

    Margaret Sunde & Colin C. F. Blake

  3. New Chemistry Laboratory, Oxford Centre for Molecular Sciences, University of Oxford, Oxford, OX1 3QT, UK

    Carol V. Robinson, Christopher M. Dobson & Sheena E. Radford

  4. Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, M5S 3H2, Canada

    Paul E. Fraser

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Booth, D., Sunde, M., Bellotti, V. et al. Instability, unfolding and aggregation of human lysozyme variants underlying amyloid fibrillogenesis. Nature 385, 787–793 (1997). https://doi.org/10.1038/385787a0

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