Structures and Activities of Prions and Prion Proteins

2010财政年度的成就：1）我们扩大了实验支持的结论，即导致传染性海绵状脑病（TSE或朊病毒病）的哺乳动物朊病毒可以单独由细菌表达的重组朊病毒蛋白产生。这一发现提供了迄今为止最令人信服的证据，证明了TSE感染因子的性质可能仅由蛋白质组成的朊病毒假说。然而，这些数据留下了其他分子强烈增强病理形式朊病毒蛋白感染滴度的可能性。2)我们已经研究了朊病毒接种的重组PrP纤维的应变依赖性结构。3)我们已经扩展了我们的表征TSE应变依赖性差异之间的相互作用朊病毒蛋白和补体因子。4)我们用红外光谱法研究了糖基化和GPI锚定对不同株羊瘙痒症朊蛋白构象的影响。5)我们研究了核酸与正常朊病毒蛋白结合的细胞效应。

Accomplishments for FY2010: 1) We have extended our experimental support for the conclusion that mammalian prions that cause a transmissible spongiform encephalopathy (TSE or prion disease) can be generated solely from bacterially expressed recombinant prion protein. This discovery provides the most compelling evidence so far for the potential protein-only prion hypothesis for the nature of the TSE infectious agent. However, the data leave open the likelihood that other molecules strongly enhance the infectious titers of pathological forms of prion protein. 2) We have studied the strain-dependent structures of prion seeded recombinant PrP fibrils. 3) We have extended our characterization of TSE strain-dependent differences in the interactions between prion protein and complement factors. 4) We have probed the effects of glycosylation and GPI-anchoring on the conformations of different strains of scrapie-prion protein by infrared spectroscopy. 5) We have studied cellular effects of nucleic acid binding to normal prion protein.