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|Title:||Crystal structure of the polymerase PAC-PB1N complex from an avian influenza H5N1 virus||Authors:||He, X.
|Issue Date:||28-Aug-2008||Citation:||He, X., Zhou, J., Bartlam, M., Zhang, R., Ma, J., Lou, Z., Li, X., Li, J., Joachimiak, A., Zeng, Z., Ge, R., Rao, Z., Liu, Y. (2008-08-28). Crystal structure of the polymerase PAC-PB1N complex from an avian influenza H5N1 virus. Nature 454 (7208) : 1123-1126. ScholarBank@NUS Repository. https://doi.org/10.1038/nature07120||Abstract:||The recent emergence of highly pathogenic avian influenza A virus strains with subtype H5N1 pose a global threat to human health. Elucidation of the underlying mechanisms of viral replication is critical for development of anti-influenza virus drugs. The influenza RNA-dependent RNA polymerase (RdRp) heterotrimer has crucial roles in viral RNA replication and transcription. It contains three proteins: PA, PB1 and PB2. PB1 harbours polymerase and endonuclease activities and PB2 is responsible for cap binding; PA is implicated in RNA replication and proteolytic activity, although its function is less clearly defined. Here we report the 2.9 ångström structure of avian H5N1 influenza A virus PA (PAC, residues 257-716) in complex with the PA-binding region of PB1 (PB1N, residues 1-25). PAC has a fold resembling a dragon's head with PB1N clamped into its open 'jaws'. PB1N is a known inhibitor that blocks assembly of the polymerase heterotrimer and abolishes viral replication. Our structure provides details for the binding of PB1N to PAC at the atomic level, demonstrating a potential target for novel anti-influenza therapeutics. We also discuss a potential nucleotide binding site and the roles of some known residues involved in polymerase activity. Furthermore, to explore the role of PA in viral replication and transcription, we propose a model for the influenza RdRp heterotrimer by comparing PAC with the λ3 reovirus polymerase structure, and docking the PAC structure into an available low resolution electron microscopy map. ©2008 Macmillan Publishers Limited. All rights reserved.||Source Title:||Nature||URI:||http://scholarbank.nus.edu.sg/handle/10635/100370||ISSN:||00280836||DOI:||10.1038/nature07120|
|Appears in Collections:||Staff Publications|
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