本帖最后由 bestar 于 2015-5-11 22:26 编辑
埃博拉病毒(EBOV)感染人类会引起致命的出血热，发病率和病死率极高。1976年人们在撒哈拉以南附近首次发现这种病毒。埃博拉病毒去年在西非造成了严重的疫情，截止到2015年4月24日，世界卫生组织(WHO)统计的总感染人数已达26,101人，死亡人数高达10,824人。目前还没有防治埃博拉病毒的疫苗和药物通过FDA的批准。 数十年来，研究者们已经确定了埃博拉病毒绝大多数蛋白的结构，除了L蛋白和核蛋白(NP)。这主要是因为这两种蛋白的表达、纯化和结晶比较困难。最近南开大学和天津国际生物医药联合研究院的研究团队揭示了埃博拉病毒NP的核心结构域，分辨率达到了1.8 Å。这一成果发表在Protein & Cell 上，文章的通讯作者是饶子和(Zihe Rao)院士和郭宇(Yu Guo)博士。 NP在埃博拉病毒的生命周期中起到了必不可少的作用，帮助病毒RNA衣壳化，形成核糖核蛋白复合体(RNP)。埃博拉病毒NP的高分辨率结构，向人们展示了它如何钳住RNA结合沟槽。这一点与其他单股负链病毒的NP类似。 这些结构信息为我们提供了宝贵的线索，有助于理解埃博拉病毒的基因组装配和转录机制。研究人员还在NP表面鉴定了一个高度保守的疏水沟槽，人们可以在此基础上开发抗病毒药物靶标埃博拉病毒的RNP形成。 原文链接： Insight into the Ebola virus nucleocapsid assembly mechanism: crystal structure of Ebola virus nucleoprotein core domain at 1.8 Å resolution. 原文摘要： Ebola virus (EBOV) is a key member of Filoviridae family and causes severe human infectious diseases with high morbidity and mortality. As a typical negative-sense single-stranded RNA (-ssRNA) viruses, EBOV possess a nucleocapsid protein (NP) to facilitate genomic RNA encapsidation to form viral ribonucleoprotein complex (RNP) together with genome RNA and polymerase, which plays the most essential role in virus proliferation cycle. However, the mechanism of EBOV RNP formation remains unclear. In this work, we solved the high resolution structure of core domain of EBOV NP. The polypeptide of EBOV NP core domain (NPcore) possesses an N-lobe and C-lobe to clamp a RNA binding groove, presenting similarities with the structures of the other reported viral NPs encoded by the members from Mononegavirales order. Most strikingly, a hydrophobic pocket at the surface of the C-lobe is occupied by an α-helix of EBOV NPcore itself, which is highly conserved among filoviridae family. Combined with other biochemical and biophysical evidences, our results provides great potential for understanding the mechanism underlying EBOV RNP formation via the mobility of EBOV NP element and enables the development of antiviral therapies targeting EBOV RNP formation.
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发表于 2015-5-11 22:22:39
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