Quiescin-sulfhydryl oxidase inhibits prion formation .

TitleQuiescin-sulfhydryl oxidase inhibits prion formation .
Publication TypeJournal Article
Year of Publication2016
AuthorsZhan, Y-A., R. Abskharon, Y. Li, J. Yuan, L. Zeng, J. Dang, M. Camacho Martinez, Z. Wang, J. Mikol, S. Lehmann, S. Bu, J. Steyaert, L. Cui, R. B. Petersen, Q. Kong, G-X. Wang, A. Wohlkonig, and W-Q. Zou
JournalAging (Albany NY)
Date Published2016 12 11
KeywordsAnimals, Brain, Cell Line, Tumor, Humans, Mice, Neuroblastoma, Oxidoreductases, Prions, Protein Folding, Scrapie

Prions are infectious proteins that cause a group of fatal transmissible diseases in animals and humans. The scrapie isoform (PrP) of the cellular prion protein (PrP) is the only known component of the prion. Several lines of evidence have suggested that the formation and molecular features of PrP are associated with an abnormal unfolding/refolding process. Quiescin-sulfhydryl oxidase (QSOX) plays a role in protein folding by introducing disulfides into unfolded reduced proteins. Here we report that QSOX inhibits human prion propagation in protein misfolding cyclic amplification reactions and murine prion propagation in scrapie-infected neuroblastoma cells. Moreover, QSOX preferentially binds PrP from prion-infected human or animal brains, but not PrP from uninfected brains. Surface plasmon resonance of the recombinant mouse PrP (moPrP) demonstrates that the affinity of QSOX for monomer is significantly lower than that for octamer (312 nM vs 1.7 nM). QSOX exhibits much lower affinity for N-terminally truncated moPrP (PrP89-230) than for the full-length moPrP (PrP23-231) (312 nM vs 2 nM), suggesting that the N-terminal region of PrP is critical for the interaction of PrP with QSOX. Our study indicates that QSOX may play a role in prion formation, which may open new therapeutic avenues for treating prion diseases.

Alternate JournalAging (Albany NY)
PubMed ID27959866
PubMed Central IDPMC5270677
Grant ListR21 NS096626 / NS / NINDS NIH HHS / United States
R01 NS062787 / NS / NINDS NIH HHS / United States
R01 NS088604 / NS / NINDS NIH HHS / United States
R21 NS087588 / NS / NINDS NIH HHS / United States
R01 NS052319 / NS / NINDS NIH HHS / United States
Research group: