| Budget Amount *help |
¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2015: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
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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. Toll-like receptors (TLRs) are examples of innate immune receptors, which sense specific molecular patterns from pathogens and activate immune responses.
TLR8 recognizes single stranded (ss) RNA derived from bacterial and viral DNA. We solved the crystal structure of TLR8 in complex with ssRNA and revealed that TLR8 is a uridine senso. TLR8 can be synergistically activated by uridine and oligonucleotide degraded from ssRNATLR9 recognizes bacterial and viral DNA containing the Cytosine-phosphate-Guanine (CpG) dideoxynucleotide motif. Here we show the crystal structure of TLR9 bound to agonistic CpG-DNA, forming a symmetric TLR9/CpG-DNA complex with 2:2 stoichiometry. CpG-DNA was recognized by both protomers in the dimer, in particular by the N-terminal fragment (LRRNT-LRR10) from one protomer and the C-terminal fragment (LRR20-LRR22) from the other.
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