Structural insight into the essential PB1-PB2 subunit contact of the influenza virus RNA polymerase
Structural insight into the essential PB1-PB2 subunit contact of the influenza virus RNA polymerase
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DOI：
10.1038/emboj.2009.138
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发表时间：
2009-06-17
期刊：
影响因子：
11.4
通讯作者：
Park, Sam-Yong
中科院分区：
文献类型：
--
作者：
Sugiyama, Kanako;Obayashi, Eiji;Park, Sam-Yong
流感病毒RNA依赖的RNA聚合酶是一种多功能异源三聚体，它使用“cap-snatching”机制产生病毒mRNA。宿主细胞mRNA被切割产生一个带帽的寡核苷酸，该寡核苷酸可以使用病毒基因组RNA作为模板进行扩展。帽结合和内切酶活性只有在病毒基因组RNA结合时才被激活。这需要从rna结合的PB1亚基向帽结合的PB2亚基发出信号，这两个亚基之间的界面对于聚合酶的活性是必不可少的。我们用蛋白质晶体学定义了这种相互作用表面，并测试了突变的接触残基对全酶功能的影响。这个新界面非常小，但它在调节250 kDa聚合酶复合体中具有关键功能，并且在禽流感病毒和人流感病毒中完全保守。EMBO杂志（2009）28,1803-1811。doi: 10.1038 / emboj.2009.138;2009年5月21日在线发布
Influenza virus RNA-dependent RNA polymerase is a multi-functional heterotrimer, which uses a 'cap-snatching' mechanism to produce viral mRNA. Host cell mRNA is cleaved to yield a cap-bearing oligonucleotide, which can be extended using viral genomic RNA as a template. The cap-binding and endonuclease activities are only activated once viral genomic RNA is bound. This requires signalling from the RNA-binding PB1 subunit to the cap-binding PB2 subunit, and the interface between these two subunits is essential for the polymerase activity. We have defined this interaction surface by protein crystallography and tested the effects of mutating contact residues on the function of the holo-enzyme. This novel interface is surprisingly small, yet, it has a crucial function in regulating the 250 kDa polymerase complex and is completely conserved among avian and human influenza viruses. The EMBO Journal (2009) 28, 1803-1811. doi:10.1038/emboj.2009.138; Published online 21 May 2009