Edited by Lewis E. Kay, University of Toronto, Toronto, ON, Canada, and approved February 2, 2021 (received for review September 17, 2020)The misfolding and aggregation into amyloid fibrils of the prion protein (PrP) have been strongly linked with a group of neurodegenerative disorders that include the mad cow disease. Currently, the molecular origins of the prion diseases are unknown, including the underlying mechanisms of PrP misfolding and the regions promoting its aggregation. Here, we identified the structural basis by which the folded domain of the human PrP converts into amyloids. We...…Edited by Lewis E. Kay, University of Toronto, Toronto, ON, Canada, and approved February 2, 2021 (received for review September 17, 2020)The misfolding and aggregation into amyloid fibrils of the prion protein (PrP) have been strongly linked with a group of neurodegenerative disorders that include the mad cow disease. Currently, the molecular origins of the prion diseases are unknown, including the underlying mechanisms of PrP misfolding and the regions promoting its aggregation. Here, we identified the structural basis by which the folded domain of the human PrP converts into amyloids. We...WW…