McKenzie D, Bartz J, Mirwald J, Olander D, Marsh R, Aiken J
Department of Animal Health and Biomedical Sciences, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
J Biol Chem. 1998 Oct 2;273(40):25545-7. doi: 10.1074/jbc.273.40.25545.
The only known difference between the cellular (PrPC) and scrapie-specific (PrPSc) isoforms of the prion protein is conformational. Because disruption of PrPSc structure decreases scrapie infectivity, restoration of the disease-specific conformation should restore infectivity. In this study, disruption of PrPSc (as monitored by the loss of proteinase K resistance) by guanidine hydrochloride (GdnHCl) resulted in decreased infectivity. Upon dilution of the GdnHCl, protease resistance of PrP was restored and infectivity was regained. The addition of copper facilitated restoration of both infectivity and protease resistance of PrP in a subset of samples that did not renature by the simple dilution of the GdnHCl. These data demonstrate that loss of scrapie infectivity can be a reversible process and that copper can enhance this restoration of proteinase K resistance and infectivity.
朊病毒蛋白的细胞型（PrPC）和瘙痒病特异性型（PrPSc）之间唯一已知的差异在于构象。由于PrPSc结构的破坏会降低瘙痒病感染性，恢复疾病特异性构象应能恢复感染性。在本研究中，盐酸胍（GdnHCl）对PrPSc的破坏（通过蛋白酶K抗性丧失监测）导致感染性降低。当GdnHCl稀释后，PrP的蛋白酶抗性得以恢复，感染性也重新获得。在一部分未通过简单稀释GdnHCl复性的样品中，添加铜促进了PrP感染性和蛋白酶抗性的恢复。这些数据表明，瘙痒病感染性的丧失可能是一个可逆过程，并且铜可以增强蛋白酶K抗性和感染性的这种恢复。
