Acid-induced molten globule state of a prion protein: crucial role of Strand 1-Helix 1-Strand 2 segment.

ABSTRACT: The conversion of a cellular prion protein (PrP(C)) to its pathogenic isoform (PrP(Sc)) is a critical event in the pathogenesis of prion diseases. Pathogenic conversion is usually associated with the oligomerization process; therefore, the conformational characteristics of the pre-oligomer state may provide insights into the conversion process. Previous studies indicate that PrP(C) is prone to oligomer formation at low pH, but the conformation of the pre-oligomer state remains unknown. In this study, we systematically analyzed the acid-induced conformational changes of PrP(C) and discovered a unique acid-induced molten globule state at pH 2.0 termed the "A-state." We characterized the structure of the A-state using far/near-UV CD, 1-anilino-8-naphthalene sulfonate fluorescence, size exclus

SUBMITTER: Honda RP 

PROVIDER: S-EPMC4215220 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature