The structural basis for an essential subunit interaction in influenza virus RNA polymerase Export

@article{citeulike:3054051, abstract = {Influenza A virus is a major human and animal pathogen with the potential to cause catastrophic loss of life. The virus reproduces rapidly, mutates frequently and occasionally crosses species barriers. The recent emergence in Asia of avian influenza related to highly pathogenic forms of the human virus has highlighted the urgent need for new effective treatments1. Here we demonstrate the importance to viral replication of a subunit interface in the viral RNA polymerase, thereby providing a new set of potential drug binding sites entirely independent of surface antigen type. No current medication targets this heterotrimeric polymerase complex. All three subunits, PB1, PB2 and PA, are required for both transcription and replication2, 3, 4. PB1 carries the polymerase active site, PB2 includes the capped-RNA recognition domain, and PA is involved in assembly of the functional complex5, 6, 7, but so far very little structural information has been reported for any of them8, 9, 10, 11. We describe the crystal structure of a large fragment of one subunit (PA) of influenza A RNA polymerase bound to a fragment of another subunit (PB1). The carboxy-terminal domain of PA forms a novel fold, and forms a deep, highly hydrophobic groove into which the amino-terminal residues of PB1 can fit by forming a 310 helix.}, author = {Obayashi, Eiji and Yoshida, Hisashi and Kawai, Fumihiro and Shibayama, Naoya and Kawaguchi, Atsushi and Nagata, Kyosuke and Tame, Jeremy R. H. and Park, Sam-Yong}, citeulike-article-id = {3054051}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/nature07225}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/nature07225}, day = {27}, doi = {10.1038/nature07225}, issn = {0028-0836}, journal = {Nature}, keywords = {polymerase, xray}, month = {July}, number = {7208}, pages = {1127--1131}, posted-at = {2009-11-10 03:33:53}, priority = {2}, publisher = {Nature Publishing Group}, title = {The structural basis for an essential subunit interaction in influenza virus RNA polymerase}, url = {http://dx.doi.org/10.1038/nature07225}, volume = {454}, year = {2008} }

TY - JOUR ID - citeulike:3054051 L3 - citeulike-article-id:3054051 N2 - Influenza A virus is a major human and animal pathogen with the potential to cause catastrophic loss of life. The virus reproduces rapidly, mutates frequently and occasionally crosses species barriers. The recent emergence in Asia of avian influenza related to highly pathogenic forms of the human virus has highlighted the urgent need for new effective treatments1. Here we demonstrate the importance to viral replication of a subunit interface in the viral RNA polymerase, thereby providing a new set of potential drug binding sites entirely independent of surface antigen type. No current medication targets this heterotrimeric polymerase complex. All three subunits, PB1, PB2 and PA, are required for both transcription and replication2, 3, 4. PB1 carries the polymerase active site, PB2 includes the capped-RNA recognition domain, and PA is involved in assembly of the functional complex5, 6, 7, but so far very little structural information has been reported for any of them8, 9, 10, 11. We describe the crystal structure of a large fragment of one subunit (PA) of influenza A RNA polymerase bound to a fragment of another subunit (PB1). The carboxy-terminal domain of PA forms a novel fold, and forms a deep, highly hydrophobic groove into which the amino-terminal residues of PB1 can fit by forming a 310 helix. IS - 7208 JF - Nature SN - 0028-0836 EP - 1131 TI - The structural basis for an essential subunit interaction in influenza virus RNA polymerase PB - Nature Publishing Group VL - 454 SP - 1127 KW - polymerase KW - xray AU - Obayashi, Eiji AU - Yoshida, Hisashi AU - Kawai, Fumihiro AU - Shibayama, Naoya AU - Kawaguchi, Atsushi AU - Nagata, Kyosuke AU - Tame, Jeremy AU - Park, Sam-Yong PY - 2008/07/27/ UR - http://dx.doi.org/10.1038/nature07225 ER -