Pressure Reveals Unique Conformational Features in Prion Protein Fibril Diversity.

ABSTRACT: The prion protein (PrP) misfolds and assembles into a wide spectrum of self-propagating quaternary structures, designated PrP^Sc. These various PrP superstructures can be functionally different, conferring clinically distinctive symptomatology, neuropathology and infectious character to the associated prion diseases. However, a satisfying molecular basis of PrP structural diversity is lacking in the literature. To provide mechanistic insights into the etiology of PrP polymorphism, we have engineered a set of 6 variants of the human protein and obtained PrP amyloid fibrils. We show that pressure induces dissociation of the fibrils, albeit with different kinetics. In addition, by focusing on the generic properties of amyloid fibrils, such as the thioflavin T binding capacities and

SUBMITTER: Torrent J 

PROVIDER: S-EPMC6391531 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature