Structural highlights
Function[PA_I33A0] Implicated in endonuclease cleavage of capped RNA primers. Displays an elongation factor activity in viral RNA synthesis. Dispensable for viral transcription, but not replication. Publication Abstract from PubMedInfluenza A viruses cause the respiratory illness influenza, which can be mild to fatal depending on the strain and host immune response. The flu polymerase acidic (PA), polymerase basic 1 (PB1), and polymerase basic 2 (PB2) proteins comprise the RNA-dependent RNA polymerase complex responsible for viral genome replication. The first crystal structures of the C-terminal domain of PA (PA-CTD) in the absence of PB1-derived peptides show a number of structural changes relative to the previously reported PB1-peptide bound structures. The human A/WSN/1933 (H1N1) and avian A/Anhui1/2013 (H7N9) strain PA-CTD proteins exhibit the same global topology as other strains in the absence of PB1, but differ extensively in the PB1 binding pocket including a widening of the binding groove and the unfolding of a beta-turn. Both PA-CTD proteins exhibited a significant increase in thermal stability in the presence of either a PB1-derived peptide or a previously reported inhibitor in differential scanning fluorimetry assays. These structural changes demonstrate plasticity in the PA-PB1 binding interface which may be exploited in the development of novel therapeutics. Structural analysis of H1N1 and H7N9 influenza A virus PA in the absence of PB1.,Moen SO, Abendroth J, Fairman JW, Baydo RO, Bullen J, Kirkwood JL, Barnes SR, Raymond AC, Begley DW, Henkel G, McCormack K, Tam VC, Phan I, Staker BL, Stacy R, Myler PJ, Lorimer D, Edwards TE Sci Rep. 2014 Aug 4;4:5944. doi: 10.1038/srep05944. PMID:25089892[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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