尼帕病毒聚合酶蛋白多聚化结构域中的一个保守碱性区域和中心环对于聚合酶功能是必需的。
A Conserved Basic Patch and Central Kink in the Nipah Virus Phosphoprotein Multimerization Domain Are Essential for Polymerase Function.
机构信息
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Viral Special Pathogens Branch, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA.
出版信息
Structure. 2019 Apr 2;27(4):660-668.e4. doi: 10.1016/j.str.2019.01.012. Epub 2019 Feb 21.
Nipah virus is a highly lethal zoonotic pathogen found in Southeast Asia that has caused human encephalitis outbreaks with 40%-70% mortality. NiV encodes its own RNA-dependent RNA polymerase within the large protein, L. Efficient polymerase activity requires the phosphoprotein, P, which tethers L to its template, the viral nucleocapsid. P is a multifunctional protein with modular domains. The central P multimerization domain is composed of a long, tetrameric coiled coil. We investigated the importance of structural features found in this domain for polymerase function using a newly constructed NiV bicistronic minigenome assay. We identified a conserved basic patch and central kink in the coiled coil that are important for polymerase function, with R555 being absolutely essential. This basic patch and central kink are conserved in the related human pathogens measles and mumps viruses, suggesting that this mechanism may be conserved.
寨卡病毒是一种高度致命的人畜共患病原体，存在于东南亚地区，已导致人类脑炎爆发，死亡率为 40%-70%。NiV 在其大蛋白 L 内编码其自身的 RNA 依赖性 RNA 聚合酶。有效的聚合酶活性需要磷蛋白 P，它将 L 连接到其模板（病毒核衣壳）上。P 是一种具有模块化结构域的多功能蛋白。中央 P 多聚化结构域由一个长的四聚体卷曲螺旋组成。我们使用新构建的 NiV 双顺反子小基因组测定法研究了该结构域中发现的结构特征对聚合酶功能的重要性。我们鉴定了卷曲螺旋中对聚合酶功能很重要的保守碱性斑和中央拐点，其中 R555 是绝对必需的。该碱性斑和中央拐点在相关的人类病原体麻疹和腮腺炎病毒中保守存在，这表明该机制可能是保守的。
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