兔子是極少數(shù)能抵抗傳染性海綿狀腦病(TSE)的哺乳動(dòng)物之一,。研究表明兔朊病毒蛋白（PrPC）與大多數(shù)哺乳動(dòng)物的PrPC不同,，它不發(fā)生PrPC→PrPSc的構(gòu)象轉(zhuǎn)變，但其分子機(jī)制尚不清楚,，預(yù)期與兔PrPC蛋白的空間結(jié)構(gòu)和動(dòng)力學(xué)特性緊密相關(guān)。
近幾年來(lái)，上海藥物所林東海課題組用多維NMR技術(shù)研究了兔PrPC(91-228)及其S173N等多個(gè)點(diǎn)突變體蛋白的溶液結(jié)構(gòu)和動(dòng)力學(xué),，發(fā)現(xiàn)兔PrPC 蛋白具有獨(dú)特的空間結(jié)構(gòu)和動(dòng)力學(xué)性質(zhì)，指出loop165-172與a3螺旋末端的相互作用以及獨(dú)特的表面電荷分布,，可能是導(dǎo)致兔朊病毒蛋白獨(dú)特的生物學(xué)功能和生化性質(zhì)的幾個(gè)主要因素,。該研究結(jié)果有助于深入地揭示朊病毒蛋白發(fā)生PrPC→PrPSc構(gòu)象變化的分子機(jī)制以及TSE的發(fā)病機(jī)理。（生物谷Bioon.com）
生物谷推薦原文出處：
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.
全文下載：
http://www.simm.ac.cn/xwzx/kydt/201008/W020100812345376131720.pdf
