Unfolded‐State Structure and Dynamics Influence the Fibril Formation of Human Prion Protein

Rigid bridges: NMR studies of the unfolded state (U) of the human prion protein (PrP) show that in the oxidized form the native disulfide bridge between two cysteine residues rigidifies the surrounding amino acids. This area is a hotspot region of the protein in terms of disease-related mutations that promote aggregation and formation of the abnormal “scrapie” form (PrPSc).