兔子是极少数能抵抗传染性海绵状脑病(TSE)的哺乳动物之一。研究表明兔朊病毒蛋白（PrPC）与大多数哺乳动物的PrPC不同，它不发生PrPC→PrPSc的构象转变，但其分子机制尚不清楚，预期与兔PrPC蛋白的空间结构和动力学特性紧密相关。
近几年来，上海药物所林东海课题组用多维NMR技术研究了兔PrPC(91-228)及其S173N等多个点突变体蛋白的溶液结构和动力学，发现兔PrPC 蛋白具有独特的空间结构和动力学性质，指出loop165-172与a3螺旋末端的相互作用以及独特的表面电荷分布，可能是导致兔朊病毒蛋白独特的生物学功能和生化性质的几个主要因素。该研究结果有助于深入地揭示朊病毒蛋白发生PrPC→PrPSc构象变化的分子机制以及TSE的发病机理。（生物谷Bioon.com）
生物谷推荐原文出处：
JBC doi: 10.1074/jbc.M110.118844
Unique Structural Characteristics of the Rabbit Prion Protein
Yi Wen1,? Jun Li1,?? Wenming Yao1, Minqian Xiong1, Jing Hong1, Yu Peng1, Gengfu Xiao2, and
Donghai Lin1,3,*
1 Shanghai Institute of Materia Medica, China;
2 Wuhan University, China
Rabbits are one of the few mammalian species that appear to be resistant to transmissible spongiform encephalopathies due to the structural characteristics of the rabbit prion protein (RaPrPC) itself. Here we determined the solution structures of the recombinant protein RaPrPC-(91-228) and its S173N variant, and detected the backbone dynamics of their structured C-terminal domains-(121-228). In contrast to many other mammalian PrPCs, loop 165-172 that connects β-sheet-2 and α-helix-2 is well-defined in RaPrPC. For the first time, order parameters S2 were obtained for residues in this loop region, indicating that loop 165-172 of RaPrPC is highly ordered. Compared with the wild-type RaPrPC, less hydrogen bonds form in the S173N variant. The NMR dynamics analysis reveals a distinct increase in the structural flexibility of loop 165-172 and helix-3 after the S173N substitution, implying that the S173N substitution disturbs the long-range interaction of loop 165-172 with helix-3, which further leads to a marked decrease in the global conformational stability. Significantly, RaPrPC possesses a unique charge distribution, carrying a continuous area of positive charges on the surface, which is distinguished from other PrPCs. The S173N substitution causes visible changes of the charge distribution around the recognition sites for the hypothetical protein X. Our results suggest that the ordered loop 165-172 and its interaction with helix-3, together with the unique distribution of surface electrostatic potential, significantly contribute to the unique structural characteristics of RaPrPC.
全文下载：
http://www.simm.ac.cn/xwzx/kydt/201008/W020100812345376131720.pdf
