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首页> 外文期刊>Nature >Crystal Structure Of An Avian Influenza Polymerase Pa_n Reveals An Endonuclease Active Site
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Crystal Structure Of An Avian Influenza Polymerase Pa_n Reveals An Endonuclease Active Site

机译：禽流感聚合酶Pa_n的晶体结构揭示了一个核酸内切酶活性位点

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The heterotrimeric influenza virus polymerase, containing the PA, PB1 and PB2 proteins, catalyses viral RNA replication and transcription in the nucleus of infected cells. PB1 holds the polymerase active site and reportedly harbours endonuclease activity, whereas PB2 is responsible for cap binding. The PA amino terminus is understood to be the major functional part of the PA protein and has been implicated in several roles, including endonuclease and protease activities as well as viral RNA/complementary RNA promoter binding. Here we report the 2.2 angstrom (A) crystal structure of the N-terminal 197 residues of PA, termed PA_N, from an avian influenza H5N1 virus. The PA_N structure has an α/β architecture and reveals a bound magnesium ion coordinated by a motif similar to the (P)DX_N(D/E)XK motif characteristic of many endonucleases. Structural comparisons and mutagenesis analysis of the motif identified in PA_N provide further evidence that PA_N holds an endonuclease active site. Furthermore, functional analysis with in vivo ribonucleoprotein reconstitution and direct in vitro endonuclease assays strongly suggest that PA_N holds the endonuclease active site and has critical roles in endonuclease activity of the influenza virus polymerase, rather than PB1. The high conservation of this endonuclease active site among influenza strains indicates that PA_N is an important target for the design of new anti-influenza therapeutics.
机译：含有PA，PB1和PB2蛋白的异三聚体流感病毒聚合酶可催化病毒RNA在感染细胞的核中复制和转录。 PB1拥有聚合酶活性位点，据报道具有内切核酸酶活性，而PB2则负责帽结合。 PA氨基末端被认为是PA蛋白的主要功能部分，并涉及多种作用，包括核酸内切酶和蛋白酶活性以及病毒RNA /互补RNA启动子结合。在这里，我们报告了禽流感H5N1病毒的PA的N末端197个残基的2.2埃（A）晶体结构，称为PA_N。 PA_N结构具有α/β结构，并显示出结合的镁离子，其基序与许多内切核酸酶的（P）DX_N（D / E）XK基序特征相似。 PA_N中鉴定的基序的结构比较和诱变分析提供了进一步的证据，证明PA_N拥有一个核酸内切酶活性位点。此外，利用体内核糖核蛋白重组和直接体外核酸内切酶测定的功能分析强烈表明，PA_N具有核酸内切酶活性位点，并且在流感病毒聚合酶而非PB1的核酸内切酶活性中具有关键作用。流感病毒株中这种核酸内切酶活性位点的高度保守性表明PA_N是设计新型抗流感治疗剂的重要目标。

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