Crystal structure of TLR13-ssRNA13 complexCrystal structure of TLR13-ssRNA13 complex

Structural highlights

4z0c is a 4 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:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TLR13_MOUSE Component of innate and adaptive immunity that recognizes and binds 23S rRNA from bacteria. TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Specifically binds the 5'-CGGAAAGACC-3' sequence on bacterial 23S rRNA, a sequence also bound by MLS group antibiotics (including erythromycin). May also recognize vesicular stomatitis virus; however, these data require additional evidences.[1] [2] [3]

Publication Abstract from PubMed

Toll-like receptors (TLRs) have crucial roles in innate immunity, functioning as pattern-recognition receptors. TLR13 recognizes a conserved sequence from bacterial 23S rRNA and then triggers an immune response. Here we report the crystal structure of the mouse TLR13 ectodomain bound by a 13-nt single-stranded (ss) RNA derived from 23S rRNA. The ssRNA induces TLR13 dimerization but assumes a stem-loop-like structure that is completely different from that in the bacterial ribosome but nevertheless is crucial for TLR13 recognition. Most of the RNA nucleotides are splayed out to make base-specific contacts with the concave surface of TLR13, and RNA-specific interactions are important to allow TLR13 to distinguish RNA from DNA. Interestingly, a viral-derived 16-nt ssRNA predicted to form a similar stem-loop-like structure also induces TLR13 activation. Together, our results reveal the structural mechanism of TLR13's sequence- and conformation-specific recognition of ssRNA.

Structural basis for specific recognition of single-stranded RNA by Toll-like receptor 13.,Song W, Wang J, Han Z, Zhang Y, Zhang H, Wang W, Chang J, Xia B, Fan S, Zhang D, Wang J, Wang HW, Chai J Nat Struct Mol Biol. 2015 Oct;22(10):782-787. doi: 10.1038/nsmb.3080. Epub 2015, Aug 31. PMID:26323037[4]

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

See Also

References

  1. Shi Z, Cai Z, Sanchez A, Zhang T, Wen S, Wang J, Yang J, Fu S, Zhang D. A novel Toll-like receptor that recognizes vesicular stomatitis virus. J Biol Chem. 2011 Feb 11;286(6):4517-24. doi: 10.1074/jbc.M110.159590. Epub 2010 , Dec 3. PMID:21131352 doi:http://dx.doi.org/10.1074/jbc.M110.159590
  2. Oldenburg M, Kruger A, Ferstl R, Kaufmann A, Nees G, Sigmund A, Bathke B, Lauterbach H, Suter M, Dreher S, Koedel U, Akira S, Kawai T, Buer J, Wagner H, Bauer S, Hochrein H, Kirschning CJ. TLR13 recognizes bacterial 23S rRNA devoid of erythromycin resistance-forming modification. Science. 2012 Aug 31;337(6098):1111-5. doi: 10.1126/science.1220363. Epub 2012, Jul 19. PMID:22821982 doi:http://dx.doi.org/10.1126/science.1220363
  3. Hidmark A, von Saint Paul A, Dalpke AH. Cutting edge: TLR13 is a receptor for bacterial RNA. J Immunol. 2012 Sep 15;189(6):2717-21. doi: 10.4049/jimmunol.1200898. Epub 2012, Aug 15. PMID:22896636 doi:http://dx.doi.org/10.4049/jimmunol.1200898
  4. Song W, Wang J, Han Z, Zhang Y, Zhang H, Wang W, Chang J, Xia B, Fan S, Zhang D, Wang J, Wang HW, Chai J. Structural basis for specific recognition of single-stranded RNA by Toll-like receptor 13. Nat Struct Mol Biol. 2015 Oct;22(10):782-787. doi: 10.1038/nsmb.3080. Epub 2015, Aug 31. PMID:26323037 doi:http://dx.doi.org/10.1038/nsmb.3080

4z0c, resolution 2.30Å

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