上海药物所林东海课题组博士生文祎等近年来用多维NMR技术研究兔朊病毒蛋白PrPC(91-228)及其S173N，I214V等点突变体蛋白的溶液结构和动力学，不久前在JBC上报道兔PrPC 蛋白具有独特的空间结构和动力学性质。
最近该课题组通过比较野生型兔PrPC与其I214V突变体的空间结构和动力学，进一步指出朊病毒蛋白的表面电荷分布和骨架柔性可能是传染性海绵状脑病(TSE)种间传播屏障的关键因素。该研究工作有助于深入理解兔朊病毒蛋白不发生PrPC→PrPSc构象变化从而不导致朊病毒病的分子机制。（生物谷Bioon.com）
生物谷推荐英文摘要：
PLoS ONE 5(10): e13273. doi:10.1371/journal.pone.0013273
Solution Structure and Dynamics of the I214V Mutant of the Rabbit Prion Protein
Yi Wen1#, Jun Li1#¤, Minqian Xiong1, Yu Peng1, Wenming Yao1, Jing Hong1, Donghai Lin1,2*
1 NMR Laboratory, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China, 2 The Key Laboratory of Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, China
Background
The conformational conversion of the host-derived cellular prion protein (PrPC) into the disease-associated scrapie isoform (PrPSc) is responsible for the pathogenesis of transmissible spongiform encephalopathies (TSEs). Various single-point mutations in PrPCs could cause structural changes and thereby distinctly influence the conformational conversion. Elucidation of the differences between the wild-type rabbit PrPC (RaPrPC) and various mutants would be of great help to understand the ability of RaPrPC to be resistant to TSE agents.
Methodology/Principal Findings
We determined the solution structure of the I214V mutant of RaPrPC(91–228) and detected the backbone dynamics of its structured C-terminal domain (121–228). The I214V mutant displays a visible shift of surface charge distribution that may have a potential effect on the binding specificity and affinity with other chaperones. The number of hydrogen bonds declines dramatically. Urea-induced transition experiments reveal an obvious decrease in the conformational stability. Furthermore, the NMR dynamics analysis discloses a significant increase in the backbone flexibility on the pico- to nanosecond time scale, indicative of lower energy barrier for structural rearrangement.
Conclusions/Significance
Our results suggest that both the surface charge distribution and the intrinsic backbone flexibility greatly contribute to species barriers for the transmission of TSEs, and thereby provide valuable hints for understanding the inability of the conformational conversion for RaPrPC.
