The stoichiometry of host PrPC glycoforms modulates the efficiency of PrPSc formation in vitro
The stoichiometry of host PrPC glycoforms modulates the efficiency of PrPSc formation in vitro
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DOI：
10.1021/bi061526k
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发表时间：
2006-11-28
期刊：
影响因子：
2.9
通讯作者：
Supattapone, Surachai
中科院分区：
文献类型：
--
作者：
Nishina, Koren A.;Deleault, Nathan R.;Supattapone, Surachai
感染性朊病毒形成的中心事件是宿主编码的糖蛋白PrPC构象变化为致病性同种型PrPSc。然而，有效的PrP转化的分子要求仍然未知。在这项研究中，我们采用最近开发的蛋白质错误折叠循环扩增（PMCA）和羊瘙痒症细胞试验（SCA）技术，研究N-连接的糖基化在体外朊病毒形成的作用。结果表明，非糖基化的PrPC分子需要繁殖小鼠RML朊病毒，而二糖基化的PrPC分子需要繁殖仓鼠Sc237朊病毒。此外，Sc237朊病毒的形成被亚化学计量水平的仓鼠非糖基化PrPC分子抑制。因此，不同的PrPC糖型之间的相互作用似乎以物种特异性的方式控制朊病毒形成的效率。
A central event in the formation of infectious prions is the conformational change of a host-encoded glycoprotein, PrPC, into a pathogenic isoform, PrPSc. However, the molecular requirements for efficient PrP conversion remain unknown. In this study, we employed the recently developed protein misfolding cyclic amplification (PMCA) and scrapie cell assay (SCA) techniques to study the role of N-linked glycosylation on prion formation in vitro. The results show that unglycosylated PrPC molecules are required to propagate mouse RML prions, whereas diglycosylated PrPC molecules are required to propagate hamster Sc237 prions. Furthermore, the formation of Sc237 prions is inhibited by substoichiometric levels of hamster unglycosylated PrPC molecules. Thus, interactions between different PrPC glycoforms appear to control the efficiency of prion formation in a species-specific manner.