5zln

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Crystal structure of mouse TLR9 in complex with two DNAs (CpG DNA and TCGCCA DNA)

Structural highlights

5zln is a 6 chain structure with sequence from Mus musculus and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.3Å
Ligands:BMA, NAG, SO4
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TLR9_MOUSE Key component of innate and adaptive immunity. TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms. TLR9 is a nucleotide-sensing TLR which is activated by unmethylated cytidine-phosphate-guanosine (CpG) dinucleotides. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Plays a role in defense against systemic mouse cytomegalovirus infection. Controls lymphocyte response to Helicobacter infection.[1] [2]

Publication Abstract from PubMed

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. TLR9 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 TLR9 activation in most vertebrate species. However, mouse TLR9 can be dimerized by CpG DNA only, although the underlying mechanism remains elusive. Here, we report the crystal structure of mouse TLR9 complexed with both DNAs. Although most TLR9-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 TLR9 dimerizes efficiently in response to CpG DNA to activate innate immunity.

Structural basis for species-specific activation of mouse Toll-like receptor 9.,Ishida H, Ohto U, Shibata T, Miyake K, Shimizu T FEBS Lett. 2018 Jul 1. doi: 10.1002/1873-3468.13176. PMID:29961984[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations
3 reviews cite this structure
Immune Sensing Mechanisms that Discriminate Self from Altered Self and Foreign Nucleic Acids.
Bartok et al. (2020)
2 more
3 other articles
No citations found

See Also

References

  1. ↑ Tabeta K, Georgel P, Janssen E, Du X, Hoebe K, Crozat K, Mudd S, Shamel L, Sovath S, Goode J, Alexopoulou L, Flavell RA, Beutler B. Toll-like receptors 9 and 3 as essential components of innate immune defense against mouse cytomegalovirus infection. Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3516-21. Epub 2004 Mar 1. PMID:14993594 doi:http://dx.doi.org/10.1073/pnas.0400525101
  2. ↑ Anderson AE, Worku ML, Khamri W, Bamford KB, Walker MM, Thursz MR. TLR9 polymorphisms determine murine lymphocyte responses to Helicobacter: results from a genome-wide scan. Eur J Immunol. 2007 Jun;37(6):1548-61. PMID:17474149 doi:http://dx.doi.org/10.1002/eji.200636562
  3. ↑ Ishida H, Ohto U, Shibata T, Miyake K, Shimizu T. Structural basis for species-specific activation of mouse Toll-like receptor 9. FEBS Lett. 2018 Jul 1. doi: 10.1002/1873-3468.13176. PMID:29961984 doi:http://dx.doi.org/10.1002/1873-3468.13176

Contents


PDB ID 5zln

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