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Structural basis for species‐specific activation of mouse Toll‐like receptor 9
Author(s) -
Ishida Hanako,
Ohto Umeharu,
Shibata Takuma,
Miyake Kensuke,
Shimizu Toshiyuki
Publication year - 2018
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13176
Subject(s) - toll like receptor , toll , receptor , chemistry , microbiology and biotechnology , basis (linear algebra) , computational biology , biology , biochemistry , immunology , innate immune system , mathematics , geometry
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. TLR 9 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 TLR 9 activation in most vertebrate species. However, mouse TLR 9 can be dimerized by CpG DNA only, although the underlying mechanism remains elusive. Here, we report the crystal structure of mouse TLR 9 complexed with both DNA s. Although most TLR 9‐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 TLR 9 dimerizes efficiently in response to CpG DNA to activate innate immunity.