4IUJ

Structure of Polymerase acid protein (PA) from Influenzavirus A Influenza A virus A, WILSON-SMITH/1933 (H1N1)

Summary for 4IUJ

• Entry DOI: 10.2210/pdb4iuj/pdb
• Descriptor: Polymerase acidic protein (2 entities in total)
• Functional Keywords: ssgcid, influenza, h1n1, structural genomics, seattle structural genomics center for infectious disease, transcription
• Biological source: Influenza A virus
• Cellular location: Host cytoplasm : P15659
• Total number of polymer chains: 1
• Total formula weight: 53096.72

Authors

Seattle Structural Genomics Center for Infectious Disease (SSGCID) (deposition date: 2013-01-21, release date: 2013-02-06, Last modification date: 2023-09-20)

Primary citation

Moen, S.O.,Abendroth, J.,Fairman, J.W.,Baydo, R.O.,Bullen, J.,Kirkwood, J.L.,Barnes, S.R.,Raymond, A.C.,Begley, D.W.,Henkel, G.,McCormack, K.,Tam, V.C.,Phan, I.,Staker, B.L.,Stacy, R.,Myler, P.J.,Lorimer, D.,Edwards, T.E.
Structural analysis of H1N1 and H7N9 influenza A virus PA in the absence of PB1.
Sci Rep, 4:5944-5944, 2014

PubMed 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 β-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.

PubMed: 25089892
DOI: 10.1038/srep05944

Experimental method

X-RAY DIFFRACTION (1.9 Å)