Identification of the single-stranded DNA recognition site on human TLR9

含未甲基化胞嘧啶-鸟嘌呤（CpG）基序的寡脱氧核苷酸（ODNs）因其与模式识别受体Toll样受体9（TLR 9）的相互作用而具有刺激天然免疫应答的潜力，已被广泛研究。通过CpG ODN激活TLR 9诱导的信号转导级联在人体的一线免疫防御中起关键作用。TLR 9的三维结构尚未报道，TLR 9的配体结合机制仍然知之甚少;因此，人TLR 9（hTLR 9）配体结合的机制需要阐明。在这项研究中，我们发现，H505，H530，和Y554是邻位取向，并形成带正电荷的簇与带负电荷的ODN可以相互作用。

Unmethylated cytosine-guanine (CpG) motif-containing oligodeoxynucleotides (ODNs) had been enormously studied for its adjuvant-potential to stimulate innate immune response via interaction with the pattern-recognition receptor Toll-like receptor 9 (TLR9). Activation of TLR9 by CpG ODN induces a signal transduction cascade that plays a pivotal role in first-line immune defense in the human body. The three-dimensional structure of TLR9 has not yet been reported, and the ligand-binding mechanism of TLR9 is still poorly understood; therefore, the mechanism of human TLR9 (hTLR9) ligand binding needs to be elucidated. In this study, we showed that H505, H530, and Y554 were vicinal-oriented and formed positively charged clusters with which negatively charged ODN could interact.