Prediction of three-dimensional structure and mapping of conformational epitopes of envelope glycoprotein of Japanese encephalitis virus
Prediction of three-dimensional structure and mapping of conformational epitopes of envelope glycoprotein of Japanese encephalitis virus
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DOI：
10.1006/viro.1999.9859
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发表时间：
1999-08-15
期刊：
影响因子：
3.7
通讯作者：
Kulkarni-Kale, U
中科院分区：
文献类型：
--
作者：
Kolaskar, AS;Kulkarni-Kale, U
日本脑炎病毒(JEV)是一种由蚊媒传播的黄病毒，是一种重要的人类病原体。包膜糖蛋白(EGP)是一种主要的结构抗原，负责病毒的血凝和诱导中和抗体。利用基于知识的同源建模方法，以森林脑炎病毒EGP的X射线结构数据为模板，预测了乙脑病毒EGP的三维结构(Rey等人，1995)。在优化的初始阶段，使用与距离相关的介电常数4r(Ij)来模拟溶剂效应。预测的结构是通过明确考虑4867个水分子将蛋白质溶解在10埃的水层中来改进的。四种独立的结构评估方法报告该结构在立体化学和几何上是可接受的。JEV的EGP具有7个β-折叠、2个α-螺旋和3个结构域的扩展结构。用水溶剂化结构描述构象表位和序列表位。这些结果证明了三级结构对于理解黄病毒，特别是乙型脑炎病毒的抗原性的重要性。该构象表位预测方法可用于识别任何已知三维结构的蛋白质抗原上的构象表位。这是最大的蛋白质之一，它的三维结构已经用同源建模方法和水作为溶剂进行了预测。(C)1999年学术出版社。
Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, is an important human pathogen. The envelope glycoprotein (Egp), a major structural antigen, is responsible for viral haemagglutination and eliciting neutralising antibodies. The three-dimensional structure of the Egp of JEV was predicted using the knowledge-based homology modeling approach and X-ray structure data of the Egp of tick-borne encephalitis virus as a template (Rey et al., 1995). In the initial stages of optimisation, a distance-dependent dielectric constant of 4r(ij) was used to simulate the solvent effect. The predicted structure was refined by solvating the protein in a 10-Angstrom layer of water by explicitly considering 4867 water molecules. Four independent structure evaluation methods report this structure to be acceptable stereochemically and geometrically. The Egp of JEV has an extended structure with seven beta-sheets, two alpha-helices, and three domains. The water-solvated structure was used to delineate conformational and sequential epitopes. These results document the importance of tertiary structure in understanding the antigenic properties of flaviviruses in general and JEV in particular. The conformational epitope prediction method could be used to identify conformational epitopes on any protein antigen with known three-dimensional structure. This is one of the largest proteins whose three-dimensional structure has been predicted using an homology modeling approach and water as a solvent. (C) 1999 Academic Press.