3WPI

Crystal structure of mouse TLR9 in complex with inhibitory DNA_super

Summary for 3WPI

• Entry DOI: 10.2210/pdb3wpi/pdb
• Related: 3WPB 3WPC 3WPD 3WPE 3WPF 3WPG 3WPH
• Descriptor: Toll-like receptor 9, DNA (5'-D(*CP*CP*TP*CP*AP*AP*TP*AP*GP*GP*GP*TP*GP*AP*GP*GP*GP*G)-3'), 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: leucine rich repeat, receptor, innate immunity, dna binding, glycosylation, cpg motif, dna binding protein-dna complex, dna binding protein/dna
• Biological source: Mus musculus (mouse); More
• Total number of polymer chains: 2
• Total formula weight: 96015.41

Authors

Ohto, U.,Shimizu, T. (deposition date: 2014-01-11, release date: 2015-02-11, Last modification date: 2024-10-16)

Primary citation

Ohto, U.,Shibata, T.,Tanji, H.,Ishida, H.,Krayukhina, E.,Uchiyama, S.,Miyake, K.,Shimizu, T.
Structural basis of CpG and inhibitory DNA recognition by Toll-like receptor 9
Nature, 520:702-705, 2015

PubMed 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.

PubMed: 25686612
DOI: 10.1038/nature14138

Experimental method

X-RAY DIFFRACTION (2.246 Å)