+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-30501 | |||||||||
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Title | Cryo-EM structure of human TLR7 in complex with UNC93B1 | |||||||||
Map data | ||||||||||
Sample |
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Function / homology | Function and homology information UNC93B1 deficiency - HSE / Toll Like Receptor 7/8 (TLR7/8) Cascade / toll-like receptor 7 signaling pathway / T cell antigen processing and presentation / I-kappaB phosphorylation / MyD88 dependent cascade initiated on endosome / TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation / Toll-like receptor binding / toll-like receptor 3 signaling pathway / toll-like receptor 9 signaling pathway ...UNC93B1 deficiency - HSE / Toll Like Receptor 7/8 (TLR7/8) Cascade / toll-like receptor 7 signaling pathway / T cell antigen processing and presentation / I-kappaB phosphorylation / MyD88 dependent cascade initiated on endosome / TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation / Toll-like receptor binding / toll-like receptor 3 signaling pathway / toll-like receptor 9 signaling pathway / siRNA binding / early phagosome / endolysosome membrane / Trafficking and processing of endosomal TLR / pattern recognition receptor activity / toll-like receptor signaling pathway / canonical NF-kappaB signal transduction / positive regulation of interferon-alpha production / positive regulation of chemokine production / positive regulation of interleukin-12 production / TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling / positive regulation of interferon-beta production / positive regulation of interleukin-8 production / regulation of protein phosphorylation / intracellular protein transport / cell morphogenesis / positive regulation of inflammatory response / positive regulation of non-canonical NF-kappaB signal transduction / cellular response to mechanical stimulus / transmembrane signaling receptor activity / antigen processing and presentation of exogenous peptide antigen via MHC class II / positive regulation of interleukin-6 production / positive regulation of type II interferon production / double-stranded RNA binding / defense response to virus / Potential therapeutics for SARS / membrane => GO:0016020 / single-stranded RNA binding / lysosome / receptor complex / endosome membrane / endosome / inflammatory response / immune response / Golgi membrane / innate immune response / endoplasmic reticulum membrane / endoplasmic reticulum / plasma membrane / cytoplasm Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.2 Å | |||||||||
Authors | Ohto U / Ishida H / Shimizu T | |||||||||
Citation | Journal: Nat Struct Mol Biol / Year: 2021 Title: Cryo-EM structures of Toll-like receptors in complex with UNC93B1. Authors: Hanako Ishida / Jinta Asami / Zhikuan Zhang / Tomohiro Nishizawa / Hideki Shigematsu / Umeharu Ohto / Toshiyuki Shimizu / Abstract: 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 ...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. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_30501.map.gz | 22 MB | EMDB map data format | |
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Header (meta data) | emd-30501-v30.xml emd-30501.xml | 11.8 KB 11.8 KB | Display Display | EMDB header |
Images | emd_30501.png | 67.3 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-30501 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-30501 | HTTPS FTP |
-Validation report
Summary document | emd_30501_validation.pdf.gz | 415.1 KB | Display | EMDB validaton report |
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Full document | emd_30501_full_validation.pdf.gz | 414.7 KB | Display | |
Data in XML | emd_30501_validation.xml.gz | 5.7 KB | Display | |
Data in CIF | emd_30501_validation.cif.gz | 6.4 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30501 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30501 | HTTPS FTP |
-Related structure data
Related structure data | 7cynMC 7c76C 7c77C M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_30501.map.gz / Format: CCP4 / Size: 30.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Voxel size | X=Y=Z: 1.245 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : Complex of TLR7 and UNC93B1
Entire | Name: Complex of TLR7 and UNC93B1 |
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Components |
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-Supramolecule #1: Complex of TLR7 and UNC93B1
Supramolecule | Name: Complex of TLR7 and UNC93B1 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Homo sapiens (human) |
-Macromolecule #1: Toll-like receptor 7
Macromolecule | Name: Toll-like receptor 7 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 121.060586 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MVFPMWTLKR QILILFNIIL ISKLLGARWF PKTLPCDVTL DVPKNHVIVD CTDKHLTEIP GGIPTNTTNL TLTINHIPDI SPASFHRLD HLVEIDFRCN CVPIPLGSKN NMCIKRLQIK PRSFSGLTYL KSLYLDGNQL LEIPQGLPPS LQLLSLEANN I FSIRKENL ...String: MVFPMWTLKR QILILFNIIL ISKLLGARWF PKTLPCDVTL DVPKNHVIVD CTDKHLTEIP GGIPTNTTNL TLTINHIPDI SPASFHRLD HLVEIDFRCN CVPIPLGSKN NMCIKRLQIK PRSFSGLTYL KSLYLDGNQL LEIPQGLPPS LQLLSLEANN I FSIRKENL TELANIEILY LGQNCYYRNP CYVSYSIEKD AFLNLTKLKV LSLKDNNVTA VPTVLPSTLT ELYLYNNMIA KI QEDDFNN LNQLQILDLS GNCPRCYNAP FPCAPCKNNS PLQIPVNAFD ALTELKVLRL HSNSLQHVPP RWFKNINKLQ ELD LSQNFL AKEIGDAKFL HFLPSLIQLD LSFNFELQVY RASMNLSQAF SSLKSLKILR IRGYVFKELK SFNLSPLHNL QNLE VLDLG TNFIKIANLS MFKQFKRLKV IDLSVNKISP SGDSSEVGFC SNARTSVESY EPQVLEQLHY FRYDKYARSC RFKNK EASF MSVNESCYKY GQTLDLSKNS IFFVKSSDFQ HLSFLKCLNL SGNLISQTLN GSEFQPLAEL RYLDFSNNRL DLLHST AFE ELHKLEVLDI SSNSHYFQSE GITHMLNFTK NLKVLQKLMM NDNDISSSTS RTMESESLRT LEFRGNHLDV LWREGDN RY LQLFKNLLKL EELDISKNSL SFLPSGVFDG MPPNLKNLSL AKNGLKSFSW KKLQCLKNLE TLDLSHNQLT TVPERLSN C SRSLKNLILK NNQIRSLTKY FLQDAFQLRY LDLSSNKIQM IQKTSFPENV LNNLKMLLLH HNRFLCTCDA VWFVWWVNH TEVTIPYLAT DVTCVGPGAH KGQSVISLDL YTCELDLTNL ILFSLSISVS LFLMVMMTAS HLYFWDVWYI YHFCKAKIKG YQRLISPDC CYDAFIVYDT KDPAVTEWVL AELVAKLEDP REKHFNLCLE ERDWLPGQPV LENLSQSIQL SKKTVFVMTD K YAKTENFK IAFYLSHQRL MDEKVDVIIL IFLEKPFQKS KFLQLRKRLC GSSVLEWPTN PQAHPYFWQC LKNALATDNH VA YSQVFKE TV |
-Macromolecule #2: Protein unc-93 homolog B1
Macromolecule | Name: Protein unc-93 homolog B1 / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 66.695969 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MEAEPPLYPM AGAAGPQGDE DLLGVPDGPE APLDELVGAY PNYNEEEEER RYYRRKRLGV LKNVLAASAG GMLTYGVYLG LLQMQLILH YDETYREVKY GNMGLPDIDS KMLMGINVTP IAALLYTPVL IRFFGTKWMM FLAVGIYALF VSTNYWERYY T LVPSAVAL ...String: MEAEPPLYPM AGAAGPQGDE DLLGVPDGPE APLDELVGAY PNYNEEEEER RYYRRKRLGV LKNVLAASAG GMLTYGVYLG LLQMQLILH YDETYREVKY GNMGLPDIDS KMLMGINVTP IAALLYTPVL IRFFGTKWMM FLAVGIYALF VSTNYWERYY T LVPSAVAL GMAIVPLWAS MGNYITRMAQ KYHEYSHYKE QDGQGMKQRP PRGSHAPYLL VFQAIFYSFF HLSFACAQLP MI YFLNHYL YDLNHTLYNV QSCGTNSHGI LSGFNKTVLR TLPRSGNLIV VESVLMAVAF LAMLLVLGLC GAAYRPTEEI DLR SVGWGN IFQLPFKHVR DYRLRHLVPF FIYSGFEVLF ACTGIALGYG VCSVGLERLA YLLVAYSLGA SAASLLGLLG LWLP RPVPL VAGAGVHLLL TFILFFWAPV PRVLQHSWIL YVAAALWGVG SALNKTGLST LLGILYEDKE RQDFIFTIYH WWQAV AIFT VYLGSSLHMK AKLAVLLVTL VAAAVSYLRM EQKLRRGVAP RQPRIPRPQH KVRGYRYLEE DNSDESDAEG EHGDGA EEE APPAGPRPGP EPAGLGRRPC PYEQAQGGDG PEEQ |
-Macromolecule #4: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 4 / Number of copies: 2 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 Details: 25 mM Hepes-NaOH, pH 7.5, 0.2 M NaCl, and 0.01% GDN |
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Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Final reconstruction | Applied symmetry - Point group: C2 (2 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 4.2 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 175000 |
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Initial angle assignment | Type: ANGULAR RECONSTITUTION |
Final angle assignment | Type: ANGULAR RECONSTITUTION |