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