5hdh: Difference between revisions
New page: '''Unreleased structure''' The entry 5hdh is ON HOLD Authors: Tanji, H., Ohto, U., Shimizu, T. Description: Crystal structure of human TLR8 with an uncleaved Z-loop [[Category: Unrelea... |
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==Crystal structure of human TLR8 with an uncleaved Z-loop== | |||
<StructureSection load='5hdh' size='340' side='right'caption='[[5hdh]], [[Resolution|resolution]] 2.60Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5hdh]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HDH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5HDH FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5hdh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hdh OCA], [https://pdbe.org/5hdh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5hdh RCSB], [https://www.ebi.ac.uk/pdbsum/5hdh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5hdh ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://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> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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. | |||
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> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5hdh" style="background-color:#fffaf0;"></div> | ||
[[Category: Shimizu | |||
[[Category: | ==See Also== | ||
*[[Toll-like Receptor 3D structures|Toll-like Receptor 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Ohto U]] | |||
[[Category: Shimizu T]] | |||
[[Category: Tanji H]] | |||
Latest revision as of 10:32, 9 August 2023
Crystal structure of human TLR8 with an uncleaved Z-loopCrystal structure of human TLR8 with an uncleaved Z-loop
Structural highlights
FunctionTLR8_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 PubMedToll-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. 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[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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