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Updated: May 14, 2026

Purification and Refolding to Amyloid Fibrils of (His)6-tagged Recombinant Shadoo Protein Expressed as Inclusion Bodies in E. coli
Published on: December 19, 2015
Conserved amyloid core structure of stop mutants of the human prion protein
1Department for NMR-based Structural Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany. Markus.Zweckstetter@dzne.de
Abstract:
Prion diseases are associated with misfolding of the natively α-helical prion protein into isoforms that are rich in cross β-structure. However, both the mechanism by which pathological conformations are produced and their structural properties remain unclear. Using a combination of nuclear magnetic resonance spectroscopy, computation, hydroxyl radical probing combined with mass-spectrometry and site-directed mutagenesis, we showed that prion stop mutants that accumulate in amyloidogenic plaque-forming aggregates fold into a β-helix. The polymorphic residue 129 is located in the hydrophobic core of the β-helix in line with a critical role of the 129 region in the packing of protein chains into prion particles. Together with electron microscopy our data support a trimeric left-handed β-helix model in which the trimer interface is formed by residues L125, Y128 and L130. Different prion types or strains might be related to different aggregate structures or filament assemblies.
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