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-Structure paper
タイトル | Structural insight into arenavirus replication machinery. |
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ジャーナル・号・ページ | Nature, Vol. 579, Issue 7800, Page 615-619, Year 2020 |
掲載日 | 2020年3月18日 |
著者 | Ruchao Peng / Xin Xu / Jiamei Jing / Min Wang / Qi Peng / Sheng Liu / Ying Wu / Xichen Bao / Peiyi Wang / Jianxun Qi / George F Gao / Yi Shi / |
PubMed 要旨 | Arenaviruses can cause severe haemorrhagic fever and neurological diseases in humans and other animals, exemplified by Lassa mammarenavirus, Machupo mammarenavirus and lymphocytic choriomeningitis ...Arenaviruses can cause severe haemorrhagic fever and neurological diseases in humans and other animals, exemplified by Lassa mammarenavirus, Machupo mammarenavirus and lymphocytic choriomeningitis virus, posing great threats to public health. These viruses encode a large multi-domain RNA-dependent RNA polymerase for transcription and replication of the viral genome. Viral polymerases are one of the leading antiviral therapeutic targets. However, the structure of arenavirus polymerase is not yet known. Here we report the near-atomic resolution structures of Lassa and Machupo virus polymerases in both apo and promoter-bound forms. These structures display a similar overall architecture to influenza virus and bunyavirus polymerases but possess unique local features, including an arenavirus-specific insertion domain that regulates the polymerase activity. Notably, the ordered active site of arenavirus polymerase is inherently switched on, without the requirement for allosteric activation by 5'-viral RNA, which is a necessity for both influenza virus and bunyavirus polymerases. Moreover, dimerization could facilitate the polymerase activity. These findings advance our understanding of the mechanism of arenavirus replication and provide an important basis for developing antiviral therapeutics. |
リンク | Nature / PubMed:32214249 |
手法 | EM (単粒子) |
解像度 | 3.58 - 7.4 Å |
構造データ | EMDB-0708: |
化合物 | ChemComp-MN: ChemComp-ZN: |
由来 |
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キーワード | VIRAL PROTEIN / polymerase / RNA virus / VIRAL PROTEIN/RNA / VIRAL PROTEIN-RNA complex |