3CM8

A RNA polymerase subunit structure from virus

Summary for 3CM8

• Entry DOI: 10.2210/pdb3cm8/pdb
• Descriptor: Polymerase acidic protein, peptide from RNA-directed RNA polymerase catalytic subunit (3 entities in total)
• Functional Keywords: protein-peptide complex, nucleotide-binding, nucleotidyltransferase, rna replication, rna-directed rna polymerase, transferase, rna binding protein-transferase complex, rna binding protein/transferase
• Biological source: Influenza A virus; More
• Cellular location: Host nucleus (Potential): Q9WLS3
• Total number of polymer chains: 2
• Total formula weight: 57065.46

Authors

He, X.,Zhou, J.,Zeng, Z.,Ma, J.,Zhang, R.,Rao, Z.,Liu, Y. (deposition date: 2008-03-21, release date: 2008-07-15, Last modification date: 2024-03-13)

Primary 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.
Crystal structure of the polymerase PAC-PB1N complex from an avian influenza H5N1 virus
Nature, 454:1123-1126, 2008

PubMed 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 (PA(C), residues 257-716) in complex with the PA-binding region of PB1 (PB1(N), residues 1-25). PA(C) has a fold resembling a dragon's head with PB1(N) clamped into its open 'jaws'. PB1(N) is a known inhibitor that blocks assembly of the polymerase heterotrimer and abolishes viral replication. Our 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. 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 PA(C) with the lambda3 reovirus polymerase structure, and docking the PA(C) structure into an available low resolution electron microscopy map.

PubMed: 18615018
DOI: 10.1038/nature07120

Experimental method

X-RAY DIFFRACTION (2.899 Å)