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近年来禽流感病毒疫情的发生给全球带来了重大威胁。对流感病毒蛋白,特别是流感病毒RNA聚合酶复合体的结构生物学研究对揭示病毒复制机制以及开展相关药物设计都具有重大意义。流感病毒RNA聚合酶是由PB1、PB2以及PA亚基组成的负责流感病毒的RNA合成以及维持病毒生命周期至关重要的分子机器。其中,PB1是该聚合酶的RNA合成亚基,PB2负责获取宿主mRNA用于病毒mRNA合成,而PA亚基功能则不清楚。本研究报道了来源于禽流感病毒RNA聚合酶PA亚基羧基端与PB1氨基端短肽复合体的三维晶体结构。该结构揭示了PA与PB1亚基相互作用方式,并分析了PA分子在RNA结合等方面的功能,对进一步研究PA功能以及开展针对聚合酶PA分子的药物设计具有十分重大的意义。
In recent years, the outbreak of the bird flu virus has brought a significant threat to the world. Structural biology studies of influenza virus proteins, particularly influenza RNA polymerase complexes, are of great importance to reveal the mechanisms of viral replication and the design of related drugs. Influenza virus RNA polymerase is the molecular machinery responsible for the RNA synthesis of influenza viruses, which consists of the PB1, PB2 and PA subunits, and is crucial for maintaining the virus’s life cycle. Among them, PB1 is the polymerase RNA synthesis subunit, PB2 is responsible for obtaining the host mRNA for viral mRNA synthesis, while the PA subunit function is not clear. In this study, we reported the three-dimensional crystal structure of the short peptide complex between the carboxyl subunit of PA subunit and the amino terminal of PB1 derived from avian influenza virus RNA polymerase. This structure reveals the interaction between PA and PB1 subunits, and analyzes the function of PA molecules in RNA binding. It is of great significance to further study the PA function and to design a drug targeting PA polymerase.