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Supplementary Fig. Finally, the source data for Supplementary Table 2 , such as the number of differing amino acids with respect to bank vole PrP, the number of rec-PrP res conformers detected, and the misfolding score, derive from the same Genbank sequences listed in Supplementary Table 1 and the gels and raw data from Figs.

Additionally, the Dataset deposited in Zenodo has been included as reference 44 in the reference list. Prion diseases are a group of rapidly progressing neurodegenerative disorders caused by the misfolding of the endogenous prion protein PrP C into a pathogenic form PrP Sc.

This process, despite being the central event underlying these disorders, remains largely unknown at a molecular level, precluding the prediction of new potential outbreaks or interspecies transmission incidents. In this work, we present a method to generate bona fide recombinant prions de novo, allowing a comprehensive analysis of protein misfolding across a wide range of prion proteins from mammalian species.