AFMB, CNRS, Université Aix-Marseille, UMR 7257, Case 925, 163 Avenue de Luminy, 13288 Marseille Cedex 09, France.
IBMM, UMR 5247 CNRS, Université de Montpellier, ENSCM, Montpellier, France.
Nucleic Acids Res. 2021 Feb 22;49(3):1737-1748. doi: 10.1093/nar/gkaa1276.
The Ebola virus is a deadly human pathogen responsible for several outbreaks in Africa. Its genome encodes the 'large' L protein, an essential enzyme that has polymerase, capping and methyltransferase activities. The methyltransferase activity leads to RNA co-transcriptional modifications at the N7 position of the cap structure and at the 2'-O position of the first transcribed nucleotide. Unlike other Mononegavirales viruses, the Ebola virus methyltransferase also catalyses 2'-O-methylation of adenosines located within the RNA sequences. Herein, we report the crystal structure at 1.8 Å resolution of the Ebola virus methyltransferase domain bound to a fragment of a camelid single-chain antibody. We identified structural determinants and key amino acids specifically involved in the internal adenosine-2'-O-methylation from cap-related methylations. These results provide the first high resolution structure of an ebolavirus L protein domain, and the framework to investigate the effects of epitranscriptomic modifications and to design possible antiviral drugs against the Filoviridae family.
埃博拉病毒是一种致命的人类病原体，导致非洲发生了几次疫情。它的基因组编码“大”L 蛋白，这是一种必需的酶，具有聚合酶、加帽和甲基转移酶活性。甲基转移酶活性导致帽结构 N7 位置和第一个转录核苷酸的 2'-O 位置的 RNA 共转录修饰。与其他单负链病毒不同，埃博拉病毒甲基转移酶还催化位于 RNA 序列内的腺苷的 2'-O-甲基化。在此，我们报告了 1.8Å分辨率的埃博拉病毒甲基转移酶结构域与骆驼科单链抗体片段结合的晶体结构。我们确定了结构决定因素和关键氨基酸，这些氨基酸专门参与帽相关甲基化中的内部腺苷-2'-O-甲基化。这些结果提供了第一个埃博拉病毒 L 蛋白结构域的高分辨率结构，并为研究转录后修饰的影响和设计针对丝状病毒科的可能抗病毒药物提供了框架。
