期刊
NATURE
卷 520, 期 7549, 页码 702-U303出版社
NATURE PORTFOLIO
DOI: 10.1038/nature14138
关键词
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资金
- Japanese Ministry of Education, Culture, Sports, Science, and Technology
- JSPS Japanese-German Graduate Externship
- Senri-Life Science Foundation
- Takeda Science Foundation
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- Grants-in-Aid for Scientific Research [26102530, 25253032] Funding Source: KAKEN
Innate immunity serves as the first line of defence 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'. TLR9 recognizes bacterial and viral DNA containing the cytosinephosphate-guanine (CpG) dideoxynucleotide moth. The molecular basis by which CpG-containing DNA (CpG-DNA) elicits immunostimulatory activity via TLR9 remains to be elucidated. Here we show the crystal structures of three forms of TLR9: unliganded, bound to agonistic CpG-DNA, and bound to inhibitory DNA (iDNA). AgonisticCpG-DNA-bound TLR9 formed a symmetric TLR9-CpG-DNA complex with 2:2 stoichiometry, whereas iDNA-bound TLR9 was a monomer. CpG-DNA was recognized by both protomers in the dimer, in particular by the amino-terminal fragment (LRRNT-LRR10) from one protomer and the carboxy-terminal fragment (LRR2O-LRR22) from the other. The iDNA, which formed a stem-loop structure suitable for binding by intramolecular base pairing, bound to the concave surface from LRR2-LRR 1 O. This structure serves as an important basis for improving our understanding of the functional mechanisms of TLR9.
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