Structural highlights
3w3m is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , , , , |
| Related: | 3w3g, 3w3j, 3w3k, 3w3l, 3w3n |
| Gene: | TLR8, UNQ249/PRO286 (Homo sapiens) |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Function
[TLR8_HUMAN] 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. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response.[1]
Publication Abstract from PubMed
Toll-like receptor 7 (TLR7) and TLR8 recognize single-stranded RNA and initiate innate immune responses. Several synthetic agonists of TLR7-TLR8 display novel therapeutic potential; however, the molecular basis for ligand recognition and activation of signaling by TLR7 or TLR8 is largely unknown. In this study, the crystal structures of unliganded and ligand-induced activated human TLR8 dimers were elucidated. Ligand recognition was mediated by a dimerization interface formed by two protomers. Upon ligand stimulation, the TLR8 dimer was reorganized such that the two C termini were brought into proximity. The loop between leucine-rich repeat 14 (LRR14) and LRR15 was cleaved; however, the N- and C-terminal halves remained associated and contributed to ligand recognition and dimerization. Thus, ligand binding induces reorganization of the TLR8 dimer, which enables downstream signaling processes.
Structural reorganization of the Toll-like receptor 8 dimer induced by agonistic ligands.,Tanji H, Ohto U, Shibata T, Miyake K, Shimizu T Science. 2013 Mar 22;339(6126):1426-9. doi: 10.1126/science.1229159. PMID:23520111[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Doyle SL, Jefferies CA, Feighery C, O'Neill LA. Signaling by Toll-like receptors 8 and 9 requires Bruton's tyrosine kinase. J Biol Chem. 2007 Dec 21;282(51):36953-60. Epub 2007 Oct 11. PMID:17932028 doi:10.1074/jbc.M707682200
- ↑ Tanji H, Ohto U, Shibata T, Miyake K, Shimizu T. Structural reorganization of the Toll-like receptor 8 dimer induced by agonistic ligands. Science. 2013 Mar 22;339(6126):1426-9. doi: 10.1126/science.1229159. PMID:23520111 doi:http://dx.doi.org/10.1126/science.1229159
