Determination of the fold of the core protein of hepatitis B virus ky electron cryomicroscopy
Determination of the fold of the core protein of hepatitis B virus ky electron cryomicroscopy
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DOI：
10.1038/386088a0
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发表时间：
1997-03-06
期刊：
影响因子：
64.8
通讯作者：
Crowther, RA
中科院分区：
文献类型：
--
作者：
Bottcher, B;Wynne, SA;Crowther, RA
乙型肝炎病毒是一种主要的人类病原体，全世界估计有3亿携带者，慢性感染可导致肝硬化和肝癌。病毒由内核衣壳或核心组成，被含有病毒编码的表面蛋白的脂质包膜包围。核心蛋白在细菌中表达时，组装成核心壳颗粒，与病毒的天然核心非常相似。在这里，我们使用电子冷冻显微镜将核心蛋白的结构解决到7.4埃的分辨率。来自34张不同离焦程度的显微照片的大约6400个单个粒子的图像被组合在一起，形成了二十面体对称。三维地图揭示了多肽链的完整折叠，这与先前解决的病毒衣壳蛋白非常不同，并且在很大程度上是α -螺旋状的。亚基的二聚体聚集在壳表面产生尖刺，尖刺由四个长α螺旋的径向束组成。我们的模型表明，与核心蛋白的免疫优势区相对应的序列位于尖刺的尖端，也解释了核心蛋白的其他特性。
Hepatitis B virus, a major human pathogen with an estimated 300 million carriers worldwide, can lead to cirrhosis and liver cancer in cases of chronic infection. The virus consists of an inner nucleocapsid or core, surrounded by a lipid envelope containing virally encoded surface proteins. The core protein, when expressed in bacteria, assembles into core shell particles, closely resembling the native core of the virus. Here we use electron cryomicroscopy to solve the structure of the core protein to 7.4 Angstrom resolution. Images of about 6,400 individual particles from 34 micrographs at different levels of defocus were combined, imposing icosahedral symmetry. The three-dimensional map reveals the complete fold of the polypeptide chain, which is quite unlike previously solved viral capsid proteins and is largely alpha-helical. The dimer clustering of subunits produces spikes on the surface of the shell, which consist of radial bundles of four long alpha-helices. Our model implies that the sequence corresponding to the immunodominant region of the core protein lies at the tip of the spike and also explains other properties of the core protein.