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

Umeharu Ohto, Takuma Shibata, Hiromi Tanji, Hanako Ishida, Elena Krayukhina, Susumu Uchiyama, Kensuke Miyake, Toshiyuki Shimizu

Research output: Contribution to journalArticlepeer-review

217 Citations (Scopus)

Abstract

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 cytosine-phosphate-guanine (CpG) dideoxynucleotide motif. 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.

Original languageEnglish
Pages (from-to)702-705
Number of pages4
JournalNature
Volume520
Issue number7549
DOIs
Publication statusPublished - 2015 Apr 30
Externally publishedYes

ASJC Scopus subject areas

  • General

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