Crystal structure of the human astrovirus capsid spike
Crystal structure of the human astrovirus capsid spike
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DOI：
10.1073/pnas.1104834108
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发表时间：
2011-08-02
影响因子：
11.1
通讯作者：
Tao, Yizhi
中科院分区：
文献类型：
--
作者：
Dong, Jinhui;Dong, Liping;Tao, Yizhi
星状病毒是单链、正义RNA病毒，感染哺乳动物和鸟类，引起胃肠炎和其他肠外疾病。临床研究已经确定星状病毒是幼儿病毒性腹泻的第二大原因。在这里，我们报告的晶体结构的人星状病毒二聚体表面尖峰确定为1.8埃的分辨率。每个刺突/突出结构域的整体结构具有独特的三层β三明治折叠，具有核心六链β桶结构，该结构也在戊型肝炎病毒衣壳突起中发现，表明这两种病毒之间的系统发育关系更密切比以前承认的。戊型肝炎病毒衣壳模型的基础上，我们进行了同源建模，并产生了一个完整的，T = 3星状病毒衣壳模型的功能显着相似的人星状病毒的冷冻电镜重建图像中观察到的。将保守残基映射到星状病毒投射结构域上揭示了具有多糖识别特征的氨基酸组成的推定受体结合位点。我们的研究结果将对未来星状病毒结构和功能的表征产生重要影响，并可能在疫苗和抗病毒药物的开发中具有实际应用。
Astroviruses are single-stranded, plus-sense RNA viruses that infect both mammals and birds, causing gastroenteritis and other extra-intestinal diseases. Clinical studies have established astroviruses as the second leading cause of viral diarrhea in young children. Here we report the crystal structure of the human astrovirus dimeric surface spike determined to 1.8-angstrom resolution. The overall structure of each spike/projection domain has a unique three-layered beta-sandwiches fold, with a core, six-stranded beta-barrel structure that is also found in the hepatitis E virus capsid protrusions, suggesting a closer phylogenetic relationship between these two viruses than previously acknowledged. Based on a hepatitis E virus capsid model, we performed homology modeling and produced a complete, T = 3 astrovirus capsid model with features remarkably similar to those observed in a cryoelectron microscopy reconstruction image of a human astrovirus. Mapping conserved residues onto the astrovirus projection domain revealed a putative receptor binding site with amino acid compositions characteristic for polysaccharide recognition. Our results will have an important impact on future characterization of astrovirus structure and function, and will likely have practical applications in the development of vaccines and antivirals.