Nishina Koren A, Deleault Nathan R, Mahal Sukhvir P, Baskakov Ilia, Luhrs Thorsten, Riek Roland, Supattapone Surachai
Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA.
Biochemistry. 2006 Nov 28;45(47):14129-39. doi: 10.1021/bi061526k.
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.
传染性朊病毒形成过程中的一个核心事件是宿主编码的糖蛋白PrPC发生构象变化，转变为致病性异构体PrPSc。然而，高效PrP转化的分子要求仍然未知。在本研究中，我们采用最近开发的蛋白质错误折叠循环扩增（PMCA）和羊瘙痒病细胞测定（SCA）技术，研究N-糖基化在体外朊病毒形成中的作用。结果表明，未糖基化的PrPC分子是传播小鼠RML朊病毒所必需的，而双糖基化的PrPC分子是传播仓鼠Sc237朊病毒所必需的。此外，仓鼠未糖基化PrPC分子的亚化学计量水平可抑制Sc237朊病毒的形成。因此，不同PrPC糖型之间的相互作用似乎以物种特异性方式控制着朊病毒形成的效率。
