The structure of the binary methyltransferase-SAH complex from Zika virus reveals a novel conformation for the mechanism of mRNA capping.
The structure of the binary methyltransferase-SAH complex from Zika virus reveals a novel conformation for the mechanism of mRNA capping.
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DOI：
10.18632/oncotarget.23223
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发表时间：
2018-01-09
期刊：
影响因子：
--
通讯作者：
Kozielski F
中科院分区：
文献类型：
--
作者：
Chatrin C;Talapatra SK;Canard B;Kozielski F
寨卡病毒是一种类似登革热和西尼罗河病毒的黄病毒，作为新兴传染病类别中的病原体构成重大风险。寨卡病毒感染通常会引起非特异性的轻微症状，但也可能表现为神经系统疾病，如格林-巴利综合征。孕妇的感染与新生儿的小头畸形有关。非结构蛋白5的甲基转移酶结构域负责5′-RNA帽的两个连续甲基化。这对于基因组稳定性、有效翻译和逃避宿主免疫反应至关重要。在这里，我们呈现了寨卡甲基转移酶结构域与甲基供体SAM及其副产物SAH复合的晶体结构。甲基转移酶-SAH二元复合物呈现“封闭”或“阻塞”状态的新构象，其将限制新RNA的结合用于加帽。我们的新结构与最近发表的寨卡甲基转移酶结构的组合和比较，为寨卡病毒mRNA加帽的结构机制提供了第一次一瞥。
Zika virus, a flavivirus like Dengue and West Nile viruses, poses a significant risk as a pathogen in the category of emerging infectious diseases. Zika infections typically cause nonspecific, mild symptoms, but can also manifest as a neurological disorder like Guillain-Barré syndrome. Infection in pregnant women is linked to microcephaly in newborn infants. The methyltransferase domain of the non-structural protein 5 is responsible for two sequential methylations of the 5′-RNA cap. This is crucial for genome stability, efficient translation, and escape from the host immune response. Here we present the crystal structures of the Zika methyltransferase domain in complex with the methyl-donor SAM and its by-product SAH. The methyltransferase-SAH binary complex presents a new conformation of a “closed” or “obstructed” state that would restrict the binding of new RNA for capping. The combination and comparison of our new structures with recently published Zika methyltransferase structures provide a first glimpse into the structural mechanism of Zika virus mRNA capping.
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