| Budget Amount *help |
¥43,290,000 (Direct Cost: ¥33,300,000、Indirect Cost: ¥9,990,000)
Fiscal Year 2018: ¥11,570,000 (Direct Cost: ¥8,900,000、Indirect Cost: ¥2,670,000)
Fiscal Year 2017: ¥13,260,000 (Direct Cost: ¥10,200,000、Indirect Cost: ¥3,060,000)
Fiscal Year 2016: ¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000)
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| Outline of Final Research Achievements |
Innate immunity serves as the first line of defense against invading pathogens such as bacteria and viruses, and active adaptive immunity. We focused on the innate immune proteins, and tried to reveal the ligand recognition and regulation mechanisms by structural studies.
We determined the crystal structure of rabbit NOD2 in an ADP-bound state. The structure reveals an inactive closed conformation. We found a hydrophobic pocket on the concave surface of the LRR domain, suitable for accommodating glycan or peptide moieties of MDP. Structural studies of TLR sensing a single-stranded nucleic acids (TLR7, 8, 9) revealed that these TLRs share common mechanism for activation mechanism. Roquin mediates mRNA degradation by recognizing the constitutive-decay element (CDE) followed by recruitment of the deadenylation machinery. Crystal structure of Roquin-RNA complex revealed that The CDE RNA, forming a stem-loop structure, bound to the positively charged surface of the ROQ domain.
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