+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-30294 | |||||||||
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Title | Cryo-EM structure of mouse TLR3 in complex with UNC93B1 | |||||||||
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Sample |
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Keywords | Toll-like receptors / UNC93B1 / MFS / IMMUNE SYSTEM | |||||||||
Function / homology | Function and homology information Trafficking and processing of endosomal TLR / type III interferon production / positive regulation of type III interferon production / response to dsRNA / T cell antigen processing and presentation / toll-like receptor 7 signaling pathway / regulation of dendritic cell cytokine production / inflammatory response to wounding / Toll-like receptor binding / toll-like receptor 3 signaling pathway ...Trafficking and processing of endosomal TLR / type III interferon production / positive regulation of type III interferon production / response to dsRNA / T cell antigen processing and presentation / toll-like receptor 7 signaling pathway / regulation of dendritic cell cytokine production / inflammatory response to wounding / Toll-like receptor binding / toll-like receptor 3 signaling pathway / necroptotic signaling pathway / toll-like receptor 9 signaling pathway / early phagosome / positive regulation of cytokine production involved in inflammatory response / positive regulation of macrophage cytokine production / cellular response to exogenous dsRNA / pattern recognition receptor activity / toll-like receptor signaling pathway / response to exogenous dsRNA / positive regulation of interferon-alpha production / antigen processing and presentation / positive regulation of type I interferon production / cellular response to interferon-beta / positive regulation of chemokine production / extrinsic apoptotic signaling pathway / JNK cascade / positive regulation of interleukin-12 production / positive regulation of interferon-beta production / positive regulation of interleukin-8 production / intracellular protein transport / positive regulation of JNK cascade / microglial cell activation / response to virus / cell morphogenesis / cellular response to type II interferon / cellular response to virus / defense response / cellular response to mechanical stimulus / positive regulation of interleukin-6 production / positive regulation of type II interferon production / positive regulation of non-canonical NF-kappaB signal transduction / male gonad development / positive regulation of angiogenesis / antigen processing and presentation of exogenous peptide antigen via MHC class II / positive regulation of tumor necrosis factor production / double-stranded RNA binding / MAPK cascade / transmembrane signaling receptor activity / cellular response to xenobiotic stimulus / signaling receptor activity / defense response to virus / positive regulation of canonical NF-kappaB signal transduction / lysosome / early endosome / endosome membrane / endosome / inflammatory response / positive regulation of apoptotic process / innate immune response / endoplasmic reticulum membrane / cell surface / endoplasmic reticulum / positive regulation of transcription by RNA polymerase II / identical protein binding / plasma membrane Similarity search - Function | |||||||||
Biological species | Mus musculoides (Temminck's mouse) / Mus musculus (house mouse) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.3 Å | |||||||||
Authors | Ohto U / Ishida H | |||||||||
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_30294.map.gz | 23.5 MB | EMDB map data format | |
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Header (meta data) | emd-30294-v30.xml emd-30294.xml | 11.3 KB 11.3 KB | Display Display | EMDB header |
Images | emd_30294.png | 34.9 KB | ||
Filedesc metadata | emd-30294.cif.gz | 5.9 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-30294 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-30294 | HTTPS FTP |
-Validation report
Summary document | emd_30294_validation.pdf.gz | 533.3 KB | Display | EMDB validaton report |
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Full document | emd_30294_full_validation.pdf.gz | 532.8 KB | Display | |
Data in XML | emd_30294_validation.xml.gz | 5.6 KB | Display | |
Data in CIF | emd_30294_validation.cif.gz | 6.4 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30294 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30294 | HTTPS FTP |
-Related structure data
Related structure data | 7c77MC 7c76C 7cynC 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_30294.map.gz / Format: CCP4 / Size: 30.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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 TLR3 and UNC93B1
Entire | Name: Complex of TLR3 and UNC93B1 |
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Components |
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-Supramolecule #1: Complex of TLR3 and UNC93B1
Supramolecule | Name: Complex of TLR3 and UNC93B1 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: Mus musculoides (Temminck's mouse) |
-Macromolecule #1: Toll-like receptor 3
Macromolecule | Name: Toll-like receptor 3 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 103.785797 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MKGCSSYLMY SFGGLLSLWI LLVSSTNQCT VRYNVADCSH LKLTHIPDDL PSNITVLNLT HNQLRRLPPT NFTRYSQLAI LDAGFNSIS KLEPELCQIL PLLKVLNLQH NELSQISDQT FVFCTNLTEL DLMSNSIHKI KSNPFKNQKN LIKLDLSHNG L SSTKLGTG ...String: MKGCSSYLMY SFGGLLSLWI LLVSSTNQCT VRYNVADCSH LKLTHIPDDL PSNITVLNLT HNQLRRLPPT NFTRYSQLAI LDAGFNSIS KLEPELCQIL PLLKVLNLQH NELSQISDQT FVFCTNLTEL DLMSNSIHKI KSNPFKNQKN LIKLDLSHNG L SSTKLGTG VQLENLQELL LAKNKILALR SEELEFLGNS SLRKLDLSSN PLKEFSPGCF QTIGKLFALL LNNAQLNPHL TE KLCWELS NTSIQNLSLA NNQLLATSES TFSGLKWTNL TQLDLSYNNL HDVGNGSFSY LPSLRYLSLE YNNIQRLSPR SFY GLSNLR YLSLKRAFTK QSVSLASHPN IDDFSFQWLK YLEYLNMDDN NIPSTKSNTF TGLVSLKYLS LSKTFTSLQT LTNE TFVSL AHSPLLTLNL TKNHISKIAN GTFSWLGQLR ILDLGLNEIE QKLSGQEWRG LRNIFEIYLS YNKYLQLSTS SFALV PSLQ RLMLRRVALK NVDISPSPFR PLRNLTILDL SNNNIANINE DLLEGLENLE ILDFQHNNLA RLWKRANPGG PVNFLK GLS HLHILNLESN GLDEIPVGVF KNLFELKSIN LGLNNLNKLE PFIFDDQTSL RSLNLQKNLI TSVEKDVFGP PFQNLNS LD MRFNPFDCTC ESISWFVNWI NQTHTNISEL STHYLCNTPH HYYGFPLKLF DTSSCKDSAP FELLFIISTS MLLVFILV V LLIHIEGWRI SFYWNVSVHR ILGFKEIDTQ AEQFEYTAYI IHAHKDRDWV WEHFSPMEEQ DQSLKFCLEE RDFEAGVLG LEAIVNSIKR SRKIIFVITH HLLKDPLCRR FKVHHAVQQA IEQNLDSIIL IFLQNIPDYK LNHALCLRRG MFKSHCILNW PVQKERINA FHHKLQVALG SRNSAH UniProtKB: Toll-like receptor 3 |
-Macromolecule #2: Protein unc-93 homolog B1
Macromolecule | Name: Protein unc-93 homolog B1 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 67.03925 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MEVEPPLYPV AGAAGPQGDE DRHGVPDGPE APLDELVGAY PNYNEEEEER RYYRRKRLGV VKNVLAASTG VTLTYGVYLG LLQMQLILH YDETYREVKY GNMGLPDIDS KMLMGINVTP IAALLYTPVL IRFFGTKWMM FLAVGIYALF VSTNYWERYY T LVPSAVAL ...String: MEVEPPLYPV AGAAGPQGDE DRHGVPDGPE APLDELVGAY PNYNEEEEER RYYRRKRLGV VKNVLAASTG VTLTYGVYLG LLQMQLILH YDETYREVKY GNMGLPDIDS KMLMGINVTP IAALLYTPVL IRFFGTKWMM FLAVGIYALF VSTNYWERYY T LVPSAVAL GMAIVPLWAS MGNYITRMSQ KYYEYSHYKE QDEQGPQQRP PRGSHAPYLL VFQAIFYSFF HLSFACAQLP MI YFLNNYL YDLNHTLINV QSCGTKSQGI LNGFNKTVLR TLPRSKNLIV VESVLMAVAF LAMLMVLGLC GAAYRPTEEI DLR SVGWGN IFQLPFKHVR DFRLRHLVPF FIYSGFEVLF ACTGFALGYG VCSMGLERLA YLLIAYSLGA SASSVLGLLG LWLP RSVPL VAGAGLHLLL TLSLFFWAPA PRVLQHSWIF YFVAALWGVG SALNKTGLST LLGILYEDKE RQDFIFTIYH WWQAV AIFV VYLGSSLPMK AKLAVLLVTL VAAAASYLWM EQKLQQGLVP RQPRIPKPQH KVRGYRYLEE DNSDESDMEG EQGQGD CAE DEAPQAGPLG AEPAGPCRKP CPYEQALGGD GPEEQ UniProtKB: Protein unc-93 homolog B1 |
-Macromolecule #5: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 5 / Number of copies: 9 / 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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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
Startup model | Type of model: PDB ENTRY PDB model - PDB ID: |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 72000 |
Initial angle assignment | Type: ANGULAR RECONSTITUTION |
Final angle assignment | Type: ANGULAR RECONSTITUTION |