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== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/TLR8_HUMAN 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.<ref>PMID:17932028</ref>
[[http://www.uniprot.org/uniprot/TLR8_HUMAN 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.<ref>PMID:17932028</ref>
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== Publication Abstract from PubMed ==
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Toll-like receptor 8 (TLR8) senses single-stranded RNA (ssRNA) and initiates innate immune responses. TLR8 requires proteolytic cleavage at the loop region (Z-loop) between leucine-rich repeat (LRR) 14 and LRR15 for its activation. However, the molecular basis of Z-loop processing remains unknown. To elucidate the mechanism of Z-loop processing, we performed biochemical and structural studies of how the Z-loop affects the function of TLR8. TLR8 with the uncleaved Z-loop is unable to form a dimer, which is essential for activation, irrespective of the presence of agonistic ligands. Crystallographic analysis revealed that the uncleaved Z-loop located on the ascending lateral face prevents the approach of the dimerization partner by steric hindrance. This autoinhibition mechanism of dimerization by the Z-loop might be occurring in the proteins of the same subfamily, TLR7 and TLR9.
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Autoinhibition and relief mechanism by the proteolytic processing of Toll-like receptor 8.,Tanji H, Ohto U, Motoi Y, Shibata T, Miyake K, Shimizu T Proc Natl Acad Sci U S A. 2016 Mar 15;113(11):3012-7. doi:, 10.1073/pnas.1516000113. Epub 2016 Feb 29. PMID:26929371<ref>PMID:26929371</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
== References ==
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Revision as of 15:38, 23 June 2016

Crystal structure of human TLR8 with an uncleaved Z-loop

5hdh, resolution 2.60Å

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