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Structural insight into cap-snatching and RNA synthesis by influenza polymerase

机译:流感聚合酶捕获帽和RNA合成的结构见解

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Influenza virus polymerase uses a capped primer, derived by 'cap-snatching' from host pre-messenger RNA, to transcribe its RNA genome into mRNA and a stuttering mechanism to generate the poly(A) tail. By contrast, genome replication is unprimed and generates exact full-length copies of the template. Here we use crystal structures of bat influenza A and human influenza B polymerases (FluA and FluB), bound to the viral RNA promoter, to give mechanistic insight into these distinct processes. In the FluA structure, a loop analogous to the priming loop of flavivirus polymerases suggests that influenza could initiate unprimed template replication by a similar mechanism. Comparing the FluA and FluB structures suggests that cap-snatching involves in situ rotation of the PB2 cap-binding domain to direct the capped primer first towards the endonuclease and then into the polymerase active site. The polymerase probably undergoes considerable conformational changes to convert the observed pre-initiation state into the active initiation and elongation states.%Stephen Cusack及同事获得了包含亚单元PA、PB1和PB2、结合到其病毒RNA启动子上的完整流感聚合酶的晶体结构。在两篇论文的第一篇当中,他们发表了来自一个蝙蝠特有的甲型流感病毒的聚合酶的结构,这种流感病毒在演化上与人类/禽类的甲型流感病毒相似。第二篇论文介绍了来自乙型流感病毒一个人类分离毒株的聚合酶的结构。这两个结构一起为流感聚合酶怎样发挥功能、为不同亚单元彼此怎样发生相互作用提供了丰富信息。
机译:流感病毒聚合酶使用从宿主信使前RNA的“帽捕捉”衍生的带帽引物,将其RNA基因组转录为mRNA,并形成一种抑制机制,以产生poly(A)尾巴。相比之下,基因组复制是无引物的,并产生模板的确切全长拷贝。在这里,我们使用与病毒RNA启动子结合的蝙蝠甲型流感病毒和人类乙型流感病毒聚合酶(FluA和FluB)的晶体结构来提供对这些不同过程的机械见解。在FluA结构中,类似于黄病毒聚合酶启动环的环表明,流感病毒可以通过类似机制启动未启动模板的复制。比较FluA和FluB结构表明,帽捕获涉及PB2帽结合结构域的原位旋转,以将帽化引物首先导向核酸内切酶,然后导向聚合酶活性位点。该聚合酶可能会经历相当大的构象变化,以将观察到的预起始状态转换为主动的起始状态和延伸状态。%Stephen Cusack和同事获得了包含亚单元PA,PB1和PB2,结合到其病毒RNA启动子上的完整流感聚合酶的晶体结构。在两篇论文的第一篇当中,他们发表了来自一个蝙蝠特有的甲型流感病毒的聚合酶的结构,这种流感病毒在进化上与人类/禽类的甲型流感病毒相似。第二篇论文介绍了来自乙型流感病毒一个人类分离毒株的聚合酶的结构。 。

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  • 来源
    《Nature》 |2014年第7531期|361-366B1|共7页
  • 作者单位

    European Molecular Biology Laboratory, Grenoble Outstation, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France,University Grenoble Alpes-Centre National de la Recherche Scientifique-EMBL Unit of Virus Host-Cell Interactions, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France;

    European Molecular Biology Laboratory, Grenoble Outstation, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France,University Grenoble Alpes-Centre National de la Recherche Scientifique-EMBL Unit of Virus Host-Cell Interactions, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France;

    European Molecular Biology Laboratory, Grenoble Outstation, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France,University Grenoble Alpes-Centre National de la Recherche Scientifique-EMBL Unit of Virus Host-Cell Interactions, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France;

    European Molecular Biology Laboratory, Grenoble Outstation, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France,University Grenoble Alpes-Centre National de la Recherche Scientifique-EMBL Unit of Virus Host-Cell Interactions, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France;

    European Molecular Biology Laboratory, Grenoble Outstation, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France,University Grenoble Alpes-Centre National de la Recherche Scientifique-EMBL Unit of Virus Host-Cell Interactions, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France;

    University Grenoble Alpes-Centre National de la Recherche Scientifique-EMBL Unit of Virus Host-Cell Interactions, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France;

    European Molecular Biology Laboratory, Grenoble Outstation, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France,University Grenoble Alpes-Centre National de la Recherche Scientifique-EMBL Unit of Virus Host-Cell Interactions, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France;

    European Molecular Biology Laboratory, Grenoble Outstation, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France,University Grenoble Alpes-Centre National de la Recherche Scientifique-EMBL Unit of Virus Host-Cell Interactions, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France;

    European Molecular Biology Laboratory, Grenoble Outstation, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France,University Grenoble Alpes-Centre National de la Recherche Scientifique-EMBL Unit of Virus Host-Cell Interactions, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France;

    University Grenoble Alpes-Centre National de la Recherche Scientifique-EMBL Unit of Virus Host-Cell Interactions, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France;

    European Molecular Biology Laboratory, Grenoble Outstation, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France,University Grenoble Alpes-Centre National de la Recherche Scientifique-EMBL Unit of Virus Host-Cell Interactions, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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