Determination of amyloid core structure using chemical shifts

Authors

  • Lukasz Skora,

    1. Max Planck Institute for Biophysical Chemistry, Am Faßberg 11, Göttingen, Germany
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  • Markus Zweckstetter

    Corresponding author
    1. Max Planck Institute for Biophysical Chemistry, Am Faßberg 11, Göttingen, Germany
    2. German Center for Neurodegenerative Diseases (DZNE), 37077 Göttingen, Germany
    • German Center for Neurodegenerative Diseases (DZNE), Göttingen, and Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany
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Abstract

Amyloid fibrils are the pathological hallmark of a large variety of neurodegenerative disorders. The structural characterization of amyloid fibrils, however, is challenging due to their non-crystalline, heterogeneous, and often dynamic nature. Thus, the structure of amyloid fibrils of many proteins is still unknown. We here show that the structure calculation program CS-Rosetta can be used to obtain insight into the core structure of amyloid fibrils. Driven by experimental solid-state NMR chemical shifts and taking into account the polymeric nature of fibrils CS-Rosetta allows modeling of the core of amyloid fibrils. Application to the Y145X stop mutant of the human prion protein reveals a left-handed β-helix

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