上海藥物所林東海課題組博士生文祎等近年來用多維NMR技術(shù)研究兔朊病毒蛋白PrPC(91-228)及其S173N，I214V等點(diǎn)突變體蛋白的溶液結(jié)構(gòu)和動力學(xué),，不久前在JBC上報道兔PrPC 蛋白具有獨(dú)特的空間結(jié)構(gòu)和動力學(xué)性質(zhì),。
最近該課題組通過比較野生型兔PrPC與其I214V突變體的空間結(jié)構(gòu)和動力學(xué)，進(jìn)一步指出朊病毒蛋白的表面電荷分布和骨架柔性可能是傳染性海綿狀腦病(TSE)種間傳播屏障的關(guān)鍵因素,。該研究工作有助于深入理解兔朊病毒蛋白不發(fā)生PrPC→PrPSc構(gòu)象變化從而不導(dǎo)致朊病毒病的分子機(jī)制。（生物谷Bioon.com）
生物谷推薦英文摘要：
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.
