4om7

Crystal structure of TIR domain of TLR6Crystal structure of TIR domain of TLR6

Structural highlights

4om7 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.204Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TLR6_HUMAN Participates in the innate immune response to Gram-positive bacteria and fungi. Specifically recognizes diacylated and, to a lesser extent, triacylated lipopeptides. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Recognizes mycoplasmal macrophage-activating lipopeptide-2kD (MALP-2), soluble tuberculosis factor (STF), phenol-soluble modulin (PSM) and B.burgdorferi outer surface protein A lipoprotein (OspA-L) cooperatively with TLR2.^[1]

Publication Abstract from PubMed

Toll-like receptors (TLRs) are responsible for recognition of particular pathogens during the innate immune response and cytoplasmic Toll/interleukin-1 receptor (TIR) domain responsible for downstream signaling. TLR6 working with TLR2 can detect bacterial lipoprotein leading signal for nuclear factor-kappaB activation for immune response. To better understand TLR-mediated signaling event in the innate immune system, in this study, we report the first crystal structure of the TIR domain of TLR6 at 2.2A resolution. Our structure reveals novel homo-dimerization interfaces, which might be a critical for the interaction with TIR-containing adaptor proteins and itself. We also report structural similarities and differences of TLR6 with those of other TIR domains, which may be functionally relevant.

Crystal Structure of TIR Domain of TLR6 Reveals Novel Dimeric Interface of TIR-TIR Interaction for Toll-Like Receptor Signaling Pathway.,Jang TH, Park HH J Mol Biol. 2014 Sep 23;426(19):3305-13. doi: 10.1016/j.jmb.2014.07.024. Epub, 2014 Jul 31. PMID:25088687^[2]

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

References

↑ Bulut Y, Faure E, Thomas L, Equils O, Arditi M. Cooperation of Toll-like receptor 2 and 6 for cellular activation by soluble tuberculosis factor and Borrelia burgdorferi outer surface protein A lipoprotein: role of Toll-interacting protein and IL-1 receptor signaling molecules in Toll-like receptor 2 signaling. J Immunol. 2001 Jul 15;167(2):987-94. PMID:11441107
↑ Jang TH, Park HH. Crystal Structure of TIR Domain of TLR6 Reveals Novel Dimeric Interface of TIR-TIR Interaction for Toll-Like Receptor Signaling Pathway. J Mol Biol. 2014 Sep 23;426(19):3305-13. doi: 10.1016/j.jmb.2014.07.024. Epub, 2014 Jul 31. PMID:25088687 doi:http://dx.doi.org/10.1016/j.jmb.2014.07.024

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OCA

[1] Bulut Y, Faure E, Thomas L, Equils O, Arditi M. Cooperation of Toll-like receptor 2 and 6 for cellular activation by soluble tuberculosis factor and Borrelia burgdorferi outer surface protein A lipoprotein: role of Toll-interacting protein and IL-1 receptor signaling molecules in Toll-like receptor 2 signaling. J Immunol. 2001 Jul 15;167(2):987-94. PMID:11441107

[2] Jang TH, Park HH. Crystal Structure of TIR Domain of TLR6 Reveals Novel Dimeric Interface of TIR-TIR Interaction for Toll-Like Receptor Signaling Pathway. J Mol Biol. 2014 Sep 23;426(19):3305-13. doi: 10.1016/j.jmb.2014.07.024. Epub, 2014 Jul 31. PMID:25088687 doi:http://dx.doi.org/10.1016/j.jmb.2014.07.024

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