The structural basis for cap binding by influenza virus polymerase subunit PB2 Export

@article{citeulike:2762772, abstract = {Influenza virus mRNAs are synthesized by the trimeric viral polymerase using short capped primers obtained by a 'cap-snatching' mechanism. The polymerase PB2 subunit binds the 5' cap of host pre-mRNAs, which are cleaved after 10–13 nucleotides by the PB1 subunit. Using a library-screening method, we identified an independently folded domain of PB2 that has specific cap binding activity. The X-ray structure of the domain with bound cap analog m7GTP at 2.3-\r{A} resolution reveals a previously unknown fold and a mode of ligand binding that is similar to, but distinct from, other cap binding proteins. Binding and functional studies with point mutants confirm that the identified site is essential for cap binding in vitro and cap-dependent transcription in vivo by the trimeric polymerase complex. These findings clarify the nature of the cap binding site in PB2 and will allow efficient structure-based design of new anti-influenza compounds inhibiting viral transcription.}, author = {Guilligay, Delphine and Tarendeau, Franck and Resa-Infante, Patricia and Coloma, Rocio and Crepin, Thibaut and Sehr, Peter and Lewis, Joe and Ruigrok, Rob W. H. and Ortin, Juan and Hart, Darren J. and Cusack, Stephen}, citeulike-article-id = {2762772}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/nsmb.1421}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/nsmb.1421}, day = {04}, doi = {10.1038/nsmb.1421}, issn = {1545-9993}, journal = {Nature Structural \& Molecular Biology}, keywords = {polymerase, xray}, month = {May}, number = {5}, pages = {500--506}, posted-at = {2009-11-10 03:34:09}, priority = {2}, publisher = {Nature Publishing Group}, title = {The structural basis for cap binding by influenza virus polymerase subunit PB2}, url = {http://dx.doi.org/10.1038/nsmb.1421}, volume = {15}, year = {2008} }

TY - JOUR ID - citeulike:2762772 L3 - citeulike-article-id:2762772 N2 - Influenza virus mRNAs are synthesized by the trimeric viral polymerase using short capped primers obtained by a 'cap-snatching' mechanism. The polymerase PB2 subunit binds the 5' cap of host pre-mRNAs, which are cleaved after 10–13 nucleotides by the PB1 subunit. Using a library-screening method, we identified an independently folded domain of PB2 that has specific cap binding activity. The X-ray structure of the domain with bound cap analog m7GTP at 2.3-Å resolution reveals a previously unknown fold and a mode of ligand binding that is similar to, but distinct from, other cap binding proteins. Binding and functional studies with point mutants confirm that the identified site is essential for cap binding in vitro and cap-dependent transcription in vivo by the trimeric polymerase complex. These findings clarify the nature of the cap binding site in PB2 and will allow efficient structure-based design of new anti-influenza compounds inhibiting viral transcription. IS - 5 JF - Nature Structural & Molecular Biology SN - 1545-9993 EP - 506 TI - The structural basis for cap binding by influenza virus polymerase subunit PB2 PB - Nature Publishing Group VL - 15 SP - 500 KW - polymerase KW - xray AU - Guilligay, Delphine AU - Tarendeau, Franck AU - Resa-Infante, Patricia AU - Coloma, Rocio AU - Crepin, Thibaut AU - Sehr, Peter AU - Lewis, Joe AU - Ruigrok, Rob AU - Ortin, Juan AU - Hart, Darren AU - Cusack, Stephen PY - 2008/05/04/ UR - http://dx.doi.org/10.1038/nsmb.1421 ER -