PDBsum entry 3wpf

DNA binding protein

PDB id: 3wpf

Contents

Protein chain

740 a.a.

Ligands

NAG ×3

SO4 ×12

Waters ×236

PDB id:

3wpf

Name:

DNA binding protein

Title:

Crystal structure of mouse tlr9 (unliganded form)

Structure:

Toll-like receptor 9. Chain: a. Fragment: extracellular domain, unp residues 26-818. Engineered: yes. Mutation: yes

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: tlr9. Expressed in: drosophila melanogaster. Expression_system_taxid: 7227. Expression_system_cell: schneider 2(s2).

Resolution:

1.96Å R-factor: 0.228 R-free: 0.265

Authors:

U.Ohto,T.Shimizu

Key ref:

U.Ohto et al. (2015). Structural basis of CpG and inhibitory DNA recognition by Toll-like receptor 9. Nature, 520, 702-705. PubMed id: 25686612 DOI: 10.1038/nature14138

Date:

11-Jan-14 Release date: 11-Feb-15

Protein chain

Q9EQU3  (TLR9_MOUSE) -  Toll-like receptor 9 from Mus musculus

Seq: 1032 a.a.

Struc: 740 a.a.*

* PDB and UniProt seqs differ at 7 residue positions (black crosses)

DOI no: 10.1038/nature14138

Nature 520:702-705 (2015)

PubMed id: 25686612

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

U.Ohto, T.Shibata, H.Tanji, H.Ishida, E.Krayukhina, S.Uchiyama, K.Miyake, T.Shimizu.

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.