Budget Amount *help |
¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000)
Fiscal Year 2011: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2010: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Fiscal Year 2009: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
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Research Abstract |
Influenza virus RNA-dependent RNA polymerase is a multi-functional heterotrimer, which uses a "cap-snatching" mechanism to produce viral mRNA. Host cell mRNA is cleaved to yield a cap-bearing oligonucleotide which can be extended using viral genomic RNA as a template. The cap binding and endonuclease activities are only activated once viral genomic RNA is bound. This requires signaling from the RNA-binding PB1 subunit to the cap-binding PB2 subunit, and the interface between these two subunits is essential for polymerase activity. We have defined this interaction surface by protein crystallography, and tested the effects of mutating contact residues on the function of the holo-enzyme. This novel interface is surprisingly small, yet it plays a crucial role in regulating the 250 kDa polymerase, and is completely conserved among avian and human influenza.
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