View source for 7cyn


==Cryo-EM structure of human TLR7 in complex with UNC93B1==
<StructureSection load='7cyn' size='340' side='right'caption='[[7cyn]], [[Resolution|resolution]] 4.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7cyn]] is a 4 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=7CYN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CYN 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]] 4.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=7cyn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cyn OCA], [https://pdbe.org/7cyn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cyn RCSB], [https://www.ebi.ac.uk/pdbsum/7cyn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cyn ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/TLR7_HUMAN TLR7_HUMAN] Systemic lupus erythematosus. The disease is caused by variants affecting the gene represented in this entry.  The disease is caused by variants affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/TLR7_HUMAN TLR7_HUMAN] Endosomal receptor that plays a key role in innate and adaptive immunity (PubMed:14976261, PubMed:32433612). Controls host immune response against pathogens through recognition of uridine-containing single strand RNAs (ssRNAs) of viral origin or guanosine analogs (PubMed:12738885, PubMed:27742543, PubMed:31608988, PubMed:32706371, PubMed:35477763). Upon binding to agonists, undergoes dimerization that brings TIR domains from the two molecules into direct contact, leading to the recruitment of TIR-containing downstream adapter MYD88 through homotypic interaction (PubMed:27742543). In turn, the Myddosome signaling complex is formed involving IRAK4, IRAK1, TRAF6, TRAF3 leading to activation of downstream transcription factors NF-kappa-B and IRF7 to induce pro-inflammatory cytokines and interferons, respectively (PubMed:27742543, PubMed:32706371).<ref>PMID:12738885</ref> <ref>PMID:14976261</ref> <ref>PMID:27742543</ref> <ref>PMID:31608988</ref> <ref>PMID:32433612</ref> <ref>PMID:32706371</ref> <ref>PMID:35477763</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Nucleic acid-sensing Toll-like receptors (TLRs) play a pivotal role in innate immunity by recognizing foreign DNA and RNA. Compartmentalization of these TLRs in the endosome limits their activation by self-derived nucleic acids and reduces the possibility of autoimmune reactions. Although chaperone Unc-93 homolog B1, TLR signaling regulator (UNC93B1) is indispensable for the trafficking of TLRs from the endoplasmic reticulum to the endosome, mechanisms of UNC93B1-mediated TLR regulation remain largely unknown. Here, we report two cryo-EM structures of human and mouse TLR3-UNC93B1 complexes and a human TLR7-UNC93B1 complex. UNC93B1 exhibits structural similarity to the major facilitator superfamily transporters. Both TLRs interact with the UNC93B1 amino-terminal six-helix bundle through their transmembrane and luminal juxtamembrane regions, but the complexes of TLR3 and TLR7 with UNC93B1 differ in their oligomerization state. The structural information provided here should aid in designing compounds to combat autoimmune diseases.

Cryo-EM structures of Toll-like receptors in complex with UNC93B1.,Ishida H, Asami J, Zhang Z, Nishizawa T, Shigematsu H, Ohto U, Shimizu T Nat Struct Mol Biol. 2021 Feb;28(2):173-180. doi: 10.1038/s41594-020-00542-w. , Epub 2021 Jan 11. PMID:33432245<ref>PMID:33432245</ref>

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

==See Also==
*[[Toll-like Receptor 3D structures|Toll-like Receptor 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Ishida H]]
[[Category: Ohto U]]
[[Category: Shimizu T]]