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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/TLR9_MOUSE 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.<ref>PMID:14993594</ref> <ref>PMID:17474149</ref> | [[http://www.uniprot.org/uniprot/TLR9_MOUSE 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.<ref>PMID:14993594</ref> <ref>PMID:17474149</ref> | ||
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== Publication Abstract from PubMed == | |||
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. | |||
Structural basis of CpG and inhibitory DNA recognition by Toll-like receptor 9.,Ohto U, Shibata T, Tanji H, Ishida H, Krayukhina E, Uchiyama S, Miyake K, Shimizu T Nature. 2015 Apr 30;520(7549):702-5. doi: 10.1038/nature14138. Epub 2015 Feb 9. PMID:25686612<ref>PMID:25686612</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
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== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 10:29, 6 May 2015
Crystal structure of mouse TLR9 (unliganded form)Crystal structure of mouse TLR9 (unliganded form)
Structural highlights
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 PubMedInnate 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. Structural basis of CpG and inhibitory DNA recognition by Toll-like receptor 9.,Ohto U, Shibata T, Tanji H, Ishida H, Krayukhina E, Uchiyama S, Miyake K, Shimizu T Nature. 2015 Apr 30;520(7549):702-5. doi: 10.1038/nature14138. Epub 2015 Feb 9. PMID:25686612[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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