Structural basis of cpg and inhibitory dna recognition by toll-like receptor 9.

• Autores: Umeharu Ohto, Takuma Shibata, Hiromi Tanji, Hanako Ishida, Elena Krayukhina, Susumu Uchiyama
• Localización: Nature: International weekly journal of science, ISSN 0028-0836, Vol. 520, Nº 7549, 2015, págs. 702-705
• Idioma: inglés
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• Resumen

  • Innate immunity serves as the first line of defence against invading pathogens such as bacteria and viruses 1. Toll-like receptors (TLRs) are examples of innate immune receptors, which sense specific molecular patterns from pathogens and activate immune responses 2. TLR9 recognizes bacterial and viral DNA containing the cytosine-phosphate-guanine (CpG) dideoxynucleotide motif 3,4. 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, 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 (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.