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寨卡病毒的3.8 Å分辨率的冷电磁结构

Devika Sirohi¹, Zhenguo Chen¹, Lei Sun¹

¹Markey Center for Structural Biology and Purdue Institute for Inflammation, Immunology and Infectious Disease, Purdue University, West Lafayette, IN 47907, USA.

Science (New York, N.Y.)

|April 2, 2016

概括

寨卡病毒的结构显示了包膜糖蛋白的变异,这可能解释了它的传播和疾病影响. 这项flavivirus研究提供了关于病毒附着和宿主细胞相互作用的见解.

科学领域:

病毒学
结构生物学
传染性疾病

背景情况:

寨卡病毒在全球迅速蔓延,因其与出生缺陷和神经综合征有关而引起关注.
寨卡病毒属于Flaviviridae家族,包括其他重要的人类病原体,如登革热,黄热病和西尼罗河病毒.

研究的目的:

确定成熟的寨卡病毒的高分辨率结构.
与其他黄病毒相比,鉴定可能解释寨卡独特的病原性质的结构差异.

主要方法:

使用冷电子显微镜 (cryo-EM) 以3. 8安格斯特罗姆分辨率解析寨卡病毒结构.
分析的重点是包膜糖蛋白及其周围区域,特别是N结合糖化部位.

主要成果:

寨卡病毒的整体结构与其他黄病毒相似.
观察到一个关键的差异是围绕着包膜糖蛋白中的Asn{154}糖化位点的~10个氨基酸.
确定了与碳水化合物部分相对应的电子密度,这表明它可能在宿主细胞附着中发挥作用.

结论:

鉴定到的结构变异,特别是在糖化部位周围,可能会影响寨卡病毒的传播效率和疾病谱.
这些发现为了解黄病毒多样性和宿主病原体相互作用提供了结构基础.

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Cryo-electron Microscopy

Cryo-electron Microscopy

Conventional electron microscopy (EM) involves dehydration, fixation, and staining of biological samples, which distorts the native state of biological molecules and results in several artifacts. Also, the high-energy electron beam damages the sample and makes it difficult to obtain high-resolution images. These issues can be addressed using cryo-EM, which uses frozen samples and gentler electron beams. The technique was developed by Jacques Dubochet, Joachim Frank, and Richard Henderson, for...