3WPI: Crystal Structure Of Mouse Tlr9 In Complex With Inhibitory Dna_super

Citation:
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.
PDB ID: 3WPIDownload
MMDB ID: 126806
PDB Deposition Date: 2014/1/11
Updated in MMDB: 2015/05
Experimental Method:
x-ray diffraction
Resolution: 2.25  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 3WPI: dimeric; determined by author and by software (PISA)
Molecular Components in 3WPI
Label Count Molecule
Protein (1 molecule)
1
Toll-like Receptor 9(Gene symbol: Tlr9)
Molecule annotation
Nucleotide(1 molecule)
1
DNA (5'- D(*cp*cp*tp*cp*ap*ap*tp*ap*gp*gp*gp*tp*gp*ap*gp*gp*gp*g)-3')
Molecule annotation
Chemical (1 molecule)
1
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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