| Budget Amount *help |
¥16,380,000 (Direct Cost: ¥12,600,000、Indirect Cost: ¥3,780,000)
Fiscal Year 2017: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
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| Outline of Final Research Achievements |
Pathogenic bacteria such as Shigella, deliver a variety of virulence factors, called effectors, into host cells via the type III secretion system. These effectors mimic or hijack host proteins and modulate host signaling pathways to promote bacterial infection. To elucidate the molecular mechanisms of Shigella flexneri effectors such as OspI and IpaH9.8, we performed the structural and functional analyses of them. OspI deamidates of Ubc13, thereby disrupting TRAF6 activation and dampening host inflammatory responses. IpaH9.8 and IpaH1.4 possessing E3 ligase activity, dampen the NF-kappaB-mediated inflammatory response. We determined the crystal structures of deamidated Ubc13 and substrate recognition domain of IpaH9.8. These structures provide the substrate recognition and inhibition mechanisms of immune response.
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