Quiescin-sulfhydryl oxidase inhibits prion formation in vitro.
Quiescin-sulfhydryl oxidase inhibits prion formation in vitro.
复制标题
静止蛋白-巯基氧化酶抑制体外朊病毒形成
DOI：
10.18632/aging.101132
复制
发表时间：
2016-12-11
期刊：
影响因子：
--
通讯作者：
Zou WQ
中科院分区：
文献类型：
--
作者：
Zhan YA;Abskharon R;Li Y;Yuan J;Zeng L;Dang J;Martinez MC;Wang Z;Mikol J;Lehmann S;Bu S;Steyaert J;Cui L;Petersen RB;Kong Q;Wang GX;Wohlkonig A;Zou WQ
朊病毒是一种感染性蛋白质，可引起动物和人类的一组致命的传染性疾病。细胞朊病毒蛋白（PrPC）的羊瘙痒病同种型（PrPSc）是朊病毒的唯一已知成分。一些证据表明，PrPSc的形成和分子特征与异常的展开/重折叠过程有关。Quiescin-sulfhydryl oxidase（QSOX）是一种通过将二硫键引入未折叠的还原蛋白质中而参与蛋白质折叠的酶。在这里，我们报告说，QSOX抑制蛋白质错误折叠循环扩增反应中的人朊病毒的繁殖和鼠朊病毒在羊瘙痒病感染的神经母细胞瘤细胞的繁殖。此外，QSOX优先结合朊病毒感染的人类或动物大脑中的PrPSc，但不结合未感染大脑中的PrPC。重组小鼠PrP（moPrP）的表面等离子体共振表明QSOX对单体的亲和力显著低于对八聚体的亲和力（312 nM vs 1.7 nM）。QSOX对N端截短的moPrP（PrP 89 -230）的亲和力远低于全长moPrP（PrP 23 -231）（312 nM vs 2 nM），表明PrP的N端区域对于PrP与QSOX的相互作用至关重要。我们的研究表明，QSOX可能在朊病毒形成中发挥作用，这可能为治疗朊病毒疾病开辟新的治疗途径。
Prions are infectious proteins that cause a group of fatal transmissible diseases in animals and humans. The scrapie isoform (PrPSc) of the cellular prion protein (PrPC) is the only known component of the prion. Several lines of evidence have suggested that the formation and molecular features of PrPSc 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 PrPSc from prion-infected human or animal brains, but not PrPC 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.