State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People's Republic of China.
Med Microbiol Immunol. 2009 Nov;198(4):239-45. doi: 10.1007/s00430-009-0120-y. Epub 2009 Jul 25.
Manganese may play some roles in the pathogenesis of prion diseases. In this study, recombinant human wild-type (WT) PrP and PrP mutants with deleted or inserted octarepeats were exposed to manganese, and their biochemical and biophysical characteristics were evaluated by proteinase K (PK) digestion, sedimentation experiments, transmission electron microscopy and circular dichroism. It demonstrated that incubation of manganese remarkably increased PK-resistances, protein aggregations and beta-sheet contents of the PrPs. Moreover, the PrP mutants of inserted or deleted octarepeats were much vulnerable to the influence of manganese, which showed obviously more aggregation and higher beta-sheet content than that of WT-PrP. It highlights that the effect of manganese on the PrP seems to lie on the incorrectness of the octarepeats numbers. The association of the octarepeats number of PrP with manganese may further provide insight into the unresolved biological function of PrP in the neurons.
锰可能在朊病毒病的发病机制中发挥作用。在这项研究中，用锰处理重组人野生型（WT）PrP 和具有八肽重复缺失或插入的 PrP 突变体，并通过蛋白酶 K（PK）消化、沉淀实验、透射电子显微镜和圆二色性评估其生化和生物物理特性。结果表明，锰孵育可显著增加 PrP 的 PK 抗性、蛋白聚集和β-折叠含量。此外，插入或缺失八肽重复的 PrP 突变体更容易受到锰的影响，其聚集程度明显更高，β-折叠含量也高于 WT-PrP。这表明锰对 PrP 的影响似乎取决于八肽重复数的不正确。PrP 的八肽重复数与锰的结合可能进一步深入了解 PrP 在神经元中的未解决的生物学功能。
