Intermolecular crosslinking of abnormal prion protein is efficiently induced by a primuline-sensitized photoreaction

Publication date: Available online 14 November 2018Source: Biochimica et Biophysica Acta (BBA) - General SubjectsAuthor(s): Kenta Teruya, Keiko Nishizawa, Ayumi Oguma, Yuji Sakasegawa, Tetsuyuki Kitamoto, Katsumi Doh-uraAbstractIn prion diseases, infectious pathogenic particles that are composed of abnormal prion proteins (PrPSc) accumulate in the brain. PrPSc is biochemically characterized by its protease-resistance core (PrPres), but its structural features have not been fully elucidated. Here, we report that primuline, a fluorescent dye with photosensitization activity, dramatically enhances UV-irradiation-induced SDS-resistant PrPSc/res oligomer formation that can be detected by immunoblot analysis of prion-infected materials. This oligomer formation occurs specifically with PrPSc/res but not with normal prion protein, and it was demonstrated using purified PrPSc/res as well as unpurified materials. The oligomer formation proceeded in both primuline-dose- and UV irradiation time-dependent manners. Treatment with urea or formic acid did not break oligomers into monomers. Neither did the presence of aromatic amino acids modify oligomer formation. Analysis with a panel of anti-prion protein antibodies showed that the antibodies against the N-terminal region of PrPres were less reactive in the dimer than the monomer. These findings suggest that the primuline-sensitized photoreaction enhances intermolecular crosslinking of PrPSc/res molecules at a hydrophobic area of the N-ter...
Source: Biochimica et Biophysica Acta (BBA) General Subjects - Category: Biochemistry Source Type: research