View source for 7wvj


==NT-mut(K117D,K139D,K145D) TLR3 -poly I:C complex==
<StructureSection load='7wvj' size='340' side='right'caption='[[7wvj]], [[Resolution|resolution]] 3.26&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7wvj]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7WVJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WVJ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.26&#8491;</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=7wvj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wvj OCA], [https://pdbe.org/7wvj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wvj RCSB], [https://www.ebi.ac.uk/pdbsum/7wvj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wvj ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/TLR3_HUMAN TLR3_HUMAN] Defects in TLR3 are associated with herpes simplex encephalitis type 2 (HSE2) [MIM:[https://omim.org/entry/613002 613002]. HSE is a rare complication of human herpesvirus 1 (HHV-1) infection, occurring in only a small minority of HHV-1 infected individuals. HSE is characterized by hemorrhagic necrosis of parts of the temporal and frontal lobes. Onset is over several days and involves fever, headache, seizures, stupor, and often coma, frequently with a fatal outcome. Note=TLR3 mutations predispose otherwise healthy individuals to isolated herpes simplex encephalitis through a mechanism that involves impaired IFNs production and reduced immune defense against viral infection in the central nervous system.<ref>PMID:17872438</ref> 
== Function ==
[https://www.uniprot.org/uniprot/TLR3_HUMAN TLR3_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. TLR3 is a nucleotide-sensing TLR which is activated by double-stranded RNA, a sign of viral infection. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response.<ref>PMID:16144834</ref> <ref>PMID:16858407</ref> <ref>PMID:16720699</ref> <ref>PMID:17178723</ref> <ref>PMID:18172197</ref> <ref>PMID:16043704</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Toll-like Receptor 3 (TLR3) initiates a potent anti-viral immune response by binding to double-stranded RNA ligands. Previous crystallographic studies showed that TLR3 forms a homodimer when bound to a 46-base pair RNA ligand. However, this short RNA fails to initiate a robust immune response. To obtain structural insights into the length dependency of TLR3 ligands, we determine the cryo-electron microscopy structure of full-length TLR3 in a complex with a synthetic RNA ligand with an average length of ~400 base pairs. In the structure, the dimeric TLR3 units are clustered along the double-stranded RNA helix in a highly organized and cooperative fashion with a uniform inter-dimer spacing of 103 angstroms. The intracellular and transmembrane domains are dispensable for the clustering because their deletion does not interfere with the cluster formation. Our structural observation suggests that ligand-induced clustering of TLR3 dimers triggers the ordered assembly of intracellular signaling adaptors and initiates a robust innate immune response.

TLR3 forms a highly organized cluster when bound to a poly(I:C) RNA ligand.,Lim CS, Jang YH, Lee GY, Han GM, Jeong HJ, Kim JW, Lee JO Nat Commun. 2022 Nov 12;13(1):6876. doi: 10.1038/s41467-022-34602-0. PMID:36371424<ref>PMID:36371424</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7wvj" style="background-color:#fffaf0;"></div>

==See Also==
*[[Toll-like Receptor 3D structures|Toll-like Receptor 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Han GM]]
[[Category: Jang YH]]
[[Category: Lee GY]]
[[Category: Lee JO]]
[[Category: Lim CS]]