http://www.jbc.org/content/early/2010/06/10/jbc.R110.117531.full.pdf+html
free full text from " specialists" from PB2, good pictures.
EMBL France
INFLUENZA A VIRUS POLYMERASE: STRUCTURAL INSIGHTS INTO REPLICATION
AND HOST ADAPTATION MECHANISMS
Boivin S, Cusack S, Ruigrok RW, Hart DJ.
EMBL, France;
Abstract
The heterotrimeric RNA-dependent RNA polymerase of influenza viruses catalyses RNA replication and transcription activities in infected cell nuclei. The nucleotide polymerization activity is common to both replication and transcription processes with an additional cap-snatching function being employed during transcription to steal short 5' capped RNA primers from host mRNAs. Cap-binding, endonuclease and polymerase activities have long been studied biochemically, but structural studies on the polymerase and its subunits has been hindered by difficulties in producing sufficient quantities of material. Recently, because of heightened effort and advances in expression and crystallisation technologies, a series of high resolution structures of individual domains has been determined. These shed light on intrinsic activities of the polymerase including cap-snatching, subunit association and nucleocytoplasmic transport, and open up the possibility of structure-guided development of new polymerase inhibitors. Furthermore, the activity of influenza polymerase is highly host and cell-type specific, being dependent on the identity of a few key amino acid positions in the different subunits, especially at the C-terminal region of PB2. New structures demonstrate the surface exposure of these residues consistent with ideas that they might modulate interactions with host-specific factors that enhance or restrict activity. Recent proteomic and genome-wide interactome and RNAi screens have begun to suggest the identities of these potential regulators of polymerase function.
free full text from " specialists" from PB2, good pictures.
EMBL France
INFLUENZA A VIRUS POLYMERASE: STRUCTURAL INSIGHTS INTO REPLICATION
AND HOST ADAPTATION MECHANISMS
Boivin S, Cusack S, Ruigrok RW, Hart DJ.
EMBL, France;
Abstract
The heterotrimeric RNA-dependent RNA polymerase of influenza viruses catalyses RNA replication and transcription activities in infected cell nuclei. The nucleotide polymerization activity is common to both replication and transcription processes with an additional cap-snatching function being employed during transcription to steal short 5' capped RNA primers from host mRNAs. Cap-binding, endonuclease and polymerase activities have long been studied biochemically, but structural studies on the polymerase and its subunits has been hindered by difficulties in producing sufficient quantities of material. Recently, because of heightened effort and advances in expression and crystallisation technologies, a series of high resolution structures of individual domains has been determined. These shed light on intrinsic activities of the polymerase including cap-snatching, subunit association and nucleocytoplasmic transport, and open up the possibility of structure-guided development of new polymerase inhibitors. Furthermore, the activity of influenza polymerase is highly host and cell-type specific, being dependent on the identity of a few key amino acid positions in the different subunits, especially at the C-terminal region of PB2. New structures demonstrate the surface exposure of these residues consistent with ideas that they might modulate interactions with host-specific factors that enhance or restrict activity. Recent proteomic and genome-wide interactome and RNAi screens have begun to suggest the identities of these potential regulators of polymerase function.