Solution structure of dengue virus capsid protein reveals another fold
Solution structure of dengue virus capsid protein reveals another fold
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DOI：
10.1073/pnas.0305892101
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发表时间：
2004-03-09
影响因子：
11.1
通讯作者：
Post, CB
中科院分区：
文献类型：
--
作者：
Ma, LX;Jones, CT;Post, CB
登革热病毒造成约5000万至1亿人感染，每年造成近24000人死亡。登革热病毒衣壳(C)蛋白对于RNA基因组的特异性包裹是必不可少的，但关于C蛋白的结构信息很少。我们报道了登革热2C蛋白200个残基的同源二聚体的溶液结构。据我们所知，该结构提供了黄病毒C蛋白的第一张3D图像，并鉴定了一个折叠，其中一个折叠包括由两对螺旋提供的大的二聚化表面，其中一对螺旋具有螺旋的特征。核磁共振结构确定涉及二级结构排序方法，以促进亚基间核Overhaser效应相互作用的分配。登革热C蛋白的二聚体具有异常高的净电荷，其结构揭示了碱性残基在蛋白质表面的不对称分布。近一半的碱性残基位于二聚体的一个面上。相反，保守的疏水区在分子相反侧的二聚体界面上形成广泛的非极表面。我们提出了一个登革热C蛋白与RNA和病毒膜相互作用的模型，该模型基于登革热C蛋白的不对称电荷分布，与以前报道的结果一致。
Dengue virus is responsible for approximate to50-100 million infections, resulting in nearly 24,000 deaths annually. The capsid (C) protein of dengue virus is essential for specific encapsidation of the RNA genome, but little structural information on the C protein is available. We report the solution structure of the 200-residue homodimer of dengue 2 C protein. The structure provides, to our knowledge, the first 3D picture of a flavivirus C protein and identifies a fold that includes a large dimerization surface contributed by two pairs of helices, one of which has characteristics of a coiled-coil. NMR structure determination involved a secondary structure sorting approach to facilitate assignment of the inter-subunit nuclear Overhauser effect interactions. The dimer of dengue C protein has an unusually high net charge, and the structure reveals an asymmetric distribution of basic residues over the surface of the protein. Nearly half of the basic residues lie along one face of the dimer. In contrast, the conserved hydrophobic region forms an extensive apolar surface at a dimer interface on the opposite side of the molecule. We propose a model for the interaction of dengue C protein with RNA and the viral membrane that is based on the asymmetric charge distribution of the protein and is consistent with previously reported results.