Fig. 4. Comparison of PrP conformation in the RML and the 263K prion fibrils.

a Polypeptide backbone superposition on the first two β-strands (N-term alignment; secondary structure not shown) of single PrP monomers from the two different strains, coloured by their deviation in distance. b Surface models showing internal gaps and the divergent angles between the N- and C-terminal lobes. c Top, multiple PrP sequence alignment coloured by conservation and annotated by mouse RML PrP sequence numbering and secondary structure. Mouse vs hamster amino acid substitutions (AAS) that underpin distinct conformations of RML and 263K fibrils are highlighted in red. Bottom, mapping of the selected AAS onto cartoon structures of RML (this study) and 263K (PDB code: 7LNA) fibrils (sticks coloured white and by heteroatom: O, red; S, yellow). Selected conserved residues, including those involved in distinct interactions due to divergent PrP folds are shown with sticks coloured as main chain and by heteroatom (N, blue; O, red; S, yellow). Red arrows indicate different folds of the C-termini, which result in divergent tips of the C-terminal lobes.