Structural basis for species-specific activation of mouse Toll-like receptor 9

Hanako Ishida, Umeharu Ohto, Takuma Shibata, Kensuke Miyake, Toshiyuki Shimizu

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Single-stranded DNA containing unmethylated cytosine-phosphate-guanine (CpG) motifs derived from microorganisms are recognized by Toll-like receptor (TLR) 9 and activate an innate immune response. TLR9 has two DNA-binding sites for CpG DNA and DNA containing cytosine at the second position from the 5′-end; both are required for efficient TLR9 activation in most vertebrate species. However, mouse TLR9 can be dimerized by CpG DNA only, although the underlying mechanism remains elusive. Here, we report the crystal structure of mouse TLR9 complexed with both DNAs. Although most TLR9-CpG DNA interactions are conserved among species, some are unique to mice and involved in species-specificity. These findings provide the structural basis for how mouse TLR9 dimerizes efficiently in response to CpG DNA to activate innate immunity.

Original languageEnglish
Pages (from-to)2636-2646
Number of pages11
JournalFEBS Letters
Volume592
Issue number15
DOIs
Publication statusPublished - 2018 Aug
Externally publishedYes

Keywords

  • X-ray crystallography
  • crystal structure
  • innate immunity
  • pathogen-associated molecular pattern
  • toll-like receptor

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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