Crystal Structure of the Polymerase PA_C-PB1_N Complex from an Avian Influenza H5N1 Virus

The recent emergence of highly pathogenic avian influenza A virus strains H5N1 pose a global threat to human health. Structural study of viral proteins especially structure of viral RNA polymerase complex is critical for elucidation of the underlying mechanisms of viral replication and development of anti-influenza virus drugs. The influenza RNA-dependent RNA polymerase (RdRp) heterotrimer is crucial for viral life cycle which is responsible for both viral RNA replication and transcription. It contains three proteins:PA,PB1 and PB2. The function of PB1 and PB2 subunits is relatively clear,while PA is implicated in RNA replication and proteolytic activity,however,its functional mechanism is less clearly defined. Recently,we reported the crystal structure of avian H5N1 influenza A virus PA (PAC) in complex with the PA-binding region of PB1 (PB1N). This structure provides details for the binding of PB1(N) to PA(C) at the atomic level,demonstrating a potential target for novel anti-influenza therapeutics. Furthermore,the potential role of PA in viral polymerase is also discussed. This is a significant breakthrough for both PA functional study and for the design of a new generation of compounds that inhibit viral RNA polymerase activity.