Observation of sequence specificity in the seeding of protein amyloid fibrils

Authors

  • Mark R.H. Krebs,

    1. Oxford Centre for Molecular Sciences, Central Chemistry Laboratory, University of Oxford, Oxford OX1 3QH, United Kingdom
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    • Present addresses: P and C Group, Cavendish Laboratory, University of Cambridge, Cambridge CB3 0HE, UK;

  • Ludmilla A. Morozova-Roche,

    1. Oxford Centre for Molecular Sciences, Central Chemistry Laboratory, University of Oxford, Oxford OX1 3QH, United Kingdom
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    • Department of Medical Biochemistry and Biophysics, Umeå University, Umeå SE 90187, Sweden;

  • Katie Daniel,

    1. Oxford Centre for Molecular Sciences, Central Chemistry Laboratory, University of Oxford, Oxford OX1 3QH, United Kingdom
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  • Carol V. Robinson,

    1. Oxford Centre for Molecular Sciences, Central Chemistry Laboratory, University of Oxford, Oxford OX1 3QH, United Kingdom
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    • Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK.

  • Christopher M. Dobson

    Corresponding author
    1. Oxford Centre for Molecular Sciences, Central Chemistry Laboratory, University of Oxford, Oxford OX1 3QH, United Kingdom
    • Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK; fax: 44 (0) 1223-763418.
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    • Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK.


Abstract

It is well established that the rate of formation of fibrils by amyloidogenic proteins is enhanced by the addition of preformed fibrils, a phenomenon known as seeding. We show that the efficiency of seeding fibril formation from solutions of hen lysozyme by a series of other proteins depends strongly on the similarity of their sequences. This observation is consistent with the importance of long-range interactions in stabilizing the core structure of amyloid fibrils and may be associated with the existence of a species barrier observed in the transmissible spongiform encephalopathies. In addition, it is consistent with the observation of a single dominant type of protein in the deposits associated with each form of amyloid disease.

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