View source for 3ulv


==Structure of quaternary complex of human TLR3ecd with three Fabs (Form2)==
<StructureSection load='3ulv' size='340' side='right'caption='[[3ulv]], [[Resolution|resolution]] 3.52&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3ulv]] is a 7 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=3ULV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ULV 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]] 3.522&#8491;</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=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=3ulv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ulv OCA], [https://pdbe.org/3ulv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ulv RCSB], [https://www.ebi.ac.uk/pdbsum/3ulv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ulv 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) recognizes dsRNA and initiates an innate immune response through the formation of a signaling unit (SU) composed of one double-stranded RNA (dsRNA) and two TLR3 molecules. We report the crystal structure of human TLR3 ectodomain (TLR3ecd) in a quaternary complex with three neutralizing Fab fragments. Fab15 binds an epitope that overlaps the C-terminal dsRNA binding site and, in biochemical assays, blocks the interaction of TLR3ecd with dsRNA, thus directly antagonizing TLR3 signaling through inhibition of SU formation. In contrast, Fab12 and Fab1068 bind TLR3ecd at sites distinct from the N- and C-terminal regions that interact with dsRNA and do not inhibit minimal SU formation with short dsRNA. Molecular modeling based on the co-structure rationalizes these observations by showing that both Fab12 and Fab1068 prevent lateral clustering of SUs along the length of the dsRNA ligand. This model is further supported by cell-based assay results using dsRNA ligands of lengths that support single and multiple SUs. Thus, their antagonism of TLR3 signaling indicates that lateral clustering of SUs is required for TLR3 signal transduction.

Lateral Clustering of TLR3:dsRNA Signaling Units Revealed by TLR3ecd:3Fabs Quaternary Structure.,Luo J, Obmolova G, Malia TJ, Wu SJ, Duffy KE, Marion JD, Bell JK, Ge P, Zhou ZH, Teplyakov A, Zhao Y, Lamb RJ, Jordan JL, San Mateo LR, Sweet RW, Gilliland GL J Mol Biol. 2012 May 9. PMID:22579623<ref>PMID:22579623</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3ulv" style="background-color:#fffaf0;"></div>

==See Also==
*[[Albumin 3D structures|Albumin 3D structures]]
*[[Toll-like Receptor 3D structures|Toll-like Receptor 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Gilliland GL]]
[[Category: Luo J]]
[[Category: Malia T]]
[[Category: Obmolova O]]
[[Category: Teplyakov A]]