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摘要 : 核苷酸感应Toll-样受体”TLR9在识别出含有微生物DNA的CpG基序之后会触发先天免疫反应。现在,Toshiyuki Shimizu及同事显示了TLR9具体是怎样识别这种免疫刺激性DNA的。

核苷酸感应Toll-样受体”TLR9在识别出含有微生物DNA的CpG基序之后会触发先天免疫反应。现在,Toshiyuki Shimizu及同事显示了TLR9具体是怎样识别这种免疫刺激性DNA的。他们提供了三种形式的TLR9 (没有配体的形式;与免疫刺激性CpG DNA相结合的形式;与抑制性DNA相结合的形式)的晶体结构,它们揭示了TLR9激发的分子基础。这些发现将有助于以TLR9为目标的抗病毒药物和其他治疗药物的开发。


Structural basis of CpG and inhibitory DNA recognition by Toll-like receptor 9


Innate immunity serves as the first line of defence against invading pathogens such as bacteria and viruses1. Toll-like receptors (TLRs) are examples of innate immune receptors, which sense specific molecular patterns from pathogens and activate immune responses2. TLR9 recognizes bacterial and viral DNA containing the cytosine–phosphate–guanine (CpG) dideoxynucleotide motif3, 4. 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). Agonistic-CpG-DNA-bound TLR9 formed a symmetric TLR9–CpG-DNA complex with 2:2 stoichiometry, wheras 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 (LRR20–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–LRR10. This structure serves as an important basis for improving our understanding of the functional mechanisms of TLR9.

来源: Nature 浏览次数:0


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