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- Title
Structural analysis of H1N1 and H7N9 influenza A virus PA in the absence of PB1.
- Authors
Moen, Spencer O.; Abendroth, Jan; Fairman, James W.; Baydo, Ruth O.; Bullen, Jameson; Kirkwood, Jennifer L.; Barnes, Steve R.; Raymond, Amy C.; Begley, Darren W.; Henkel, Greg; McCormack, Ken; Tam, Vincent C.; Phan, Isabelle; Staker, Bart L.; Stacy, Robin; Myler, Peter J.; Lorimer, Don; Edwards, Thomas E.
- Abstract
Influenza 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 b-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.
- Subjects
INFLUENZA A virus, H1N1 subtype; H7N9 Influenza; RESPIRATORY infections; IMMUNE response; IMMUNOREGULATION; POLYMERASE genetics; GENETICS; INFECTIOUS disease transmission
- Publication
Scientific Reports, 2014, p1
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/srep05944