[English] 日本語
Yorodumi
- EMDB-30293: Cryo-EM structure of human TLR3 in complex with UNC93B1 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-30293
TitleCryo-EM structure of human TLR3 in complex with UNC93B1
Map data
Sample
  • Complex: Complex of TLR3 and UNC93B1
    • Protein or peptide: Toll-like receptor 3
    • Protein or peptide: Protein unc-93 homolog B1
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
KeywordsToll-like receptors / UNC93B1 / MFS / IMMUNE SYSTEM
Function / homology
Function and homology information


TLR3 deficiency - HSE / UNC93B1 deficiency - HSE / TICAM1 deficiency - HSE / type III interferon production / positive regulation of type III interferon production / response to dsRNA / TRAF3 deficiency - HSE / T cell antigen processing and presentation / toll-like receptor 7 signaling pathway / regulation of dendritic cell cytokine production ...TLR3 deficiency - HSE / UNC93B1 deficiency - HSE / TICAM1 deficiency - HSE / type III interferon production / positive regulation of type III interferon production / response to dsRNA / TRAF3 deficiency - HSE / T cell antigen processing and presentation / toll-like receptor 7 signaling pathway / regulation of dendritic cell cytokine production / Toll Like Receptor 3 (TLR3) Cascade / I-kappaB phosphorylation / TLR3-mediated TICAM1-dependent programmed cell death / inflammatory response to wounding / Toll-like receptor binding / toll-like receptor 3 signaling pathway / activation of NF-kappaB-inducing kinase activity / necroptotic signaling pathway / detection of virus / toll-like receptor 9 signaling pathway / endolysosome membrane / RIP-mediated NFkB activation via ZBP1 / early phagosome / hyperosmotic response / positive regulation of cytokine production involved in inflammatory response / Trafficking and processing of endosomal TLR / positive regulation of macrophage cytokine production / cellular response to exogenous dsRNA / pattern recognition receptor activity / toll-like receptor signaling pathway / RSV-host interactions / response to exogenous dsRNA / negative regulation of osteoclast differentiation / positive regulation of interferon-alpha production / cellular response to interferon-beta / positive regulation of chemokine production / JNK cascade / extrinsic apoptotic signaling pathway / TICAM1,TRAF6-dependent induction of TAK1 complex / Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation / positive regulation of interleukin-12 production / TICAM1-dependent activation of IRF3/IRF7 / positive regulation of interferon-beta production / extracellular matrix / TICAM1, RIP1-mediated IKK complex recruitment / positive regulation of interleukin-8 production / intracellular protein transport / positive regulation of JNK cascade / microglial cell activation / cell morphogenesis / cellular response to virus / cellular response to type II interferon / cellular response to mechanical stimulus / positive regulation of inflammatory response / positive regulation of interleukin-6 production / positive regulation of non-canonical NF-kappaB signal transduction / positive regulation of type II interferon production / positive regulation of angiogenesis / male gonad development / antigen processing and presentation of exogenous peptide antigen via MHC class II / positive regulation of tumor necrosis factor production / double-stranded RNA binding / 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 / defense response to bacterium / positive regulation of apoptotic process / lysosomal membrane / Golgi membrane / innate immune response / endoplasmic reticulum membrane / positive regulation of gene expression / endoplasmic reticulum / signal transduction / positive regulation of transcription by RNA polymerase II / extracellular space / identical protein binding / membrane / plasma membrane / cytoplasm
Similarity search - Function
Protein unc-93 homolog B1 / Toll-like receptor 3 trans-membrane domain / Toll-like receptor 3 trans-membrane domain / Toll-like receptor / Leucine Rich repeat / TIR domain / Cysteine-rich flanking region, C-terminal / Leucine rich repeat C-terminal domain / Toll - interleukin 1 - resistance / TIR domain profile. ...Protein unc-93 homolog B1 / Toll-like receptor 3 trans-membrane domain / Toll-like receptor 3 trans-membrane domain / Toll-like receptor / Leucine Rich repeat / TIR domain / Cysteine-rich flanking region, C-terminal / Leucine rich repeat C-terminal domain / Toll - interleukin 1 - resistance / TIR domain profile. / Leucine-rich repeat, SDS22-like subfamily / Toll/interleukin-1 receptor homology (TIR) domain / Toll/interleukin-1 receptor homology (TIR) domain superfamily / Leucine rich repeat / Leucine-rich repeat, typical subtype / Leucine-rich repeats, typical (most populated) subfamily / Leucine-rich repeat profile. / Leucine-rich repeat / Leucine-rich repeat domain superfamily
Similarity search - Domain/homology
Toll-like receptor 3 / Protein unc-93 homolog B1
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.4 Å
AuthorsOhto U / Ishida H
CitationJournal: 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
DepositionMay 23, 2020-
Header (metadata) releaseJan 6, 2021-
Map releaseJan 6, 2021-
UpdateOct 23, 2024-
Current statusOct 23, 2024Processing site: PDBj / Status: Released

-
Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.01
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by height
  • Surface level: 0.01
  • Imaged by UCSF Chimera
  • Download
  • Surface view with fitted model
  • Atomic models: PDB-7c76
  • Surface level: 0.01
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_30293.png

Downloads & links

-
Map

FileDownload / File: emd_30293.map.gz / Format: CCP4 / Size: 30.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.25 Å/pix.
x 200 pix.
= 249. Å		1.25 Å/pix.
x 200 pix.
= 249. Å		1.25 Å/pix.
x 200 pix.
= 249. Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.245 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.01 / Movie #1: 0.01
Minimum - Maximum-0.05652513 - 0.08478708
Average (Standard dev.)-0.00000064713913 (±0.002289599)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions200200200
Spacing200200200
CellA=B=C: 249.0 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.2451.2451.245
M x/y/z200200200
origin x/y/z0.0000.0000.000
length x/y/z249.000249.000249.000
α/β/γ90.00090.00090.000
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS200200200
D min/max/mean-0.0570.085-0.000

-
Supplemental data

-
Sample components

-
Entire : Complex of TLR3 and UNC93B1

EntireName: Complex of TLR3 and UNC93B1
Components
  • Complex: Complex of TLR3 and UNC93B1
    • Protein or peptide: Toll-like receptor 3
    • Protein or peptide: Protein unc-93 homolog B1
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

-
Supramolecule #1: Complex of TLR3 and UNC93B1

SupramoleculeName: Complex of TLR3 and UNC93B1 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2
Source (natural)Organism: Homo sapiens (human)

-
Macromolecule #1: Toll-like receptor 3

MacromoleculeName: Toll-like receptor 3 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 103.94632 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MRQTLPCIYF WGGLLPFGML CASSTTKCTV SHEVADCSHL KLTQVPDDLP TNITVLNLTH NQLRRLPAAN FTRYSQLTSL DVGFNTISK LEPELCQKLP MLKVLNLQHN ELSQLSDKTF AFCTNLTELH LMSNSIQKIK NNPFVKQKNL ITLDLSHNGL S STKLGTQV ...String:
MRQTLPCIYF WGGLLPFGML CASSTTKCTV SHEVADCSHL KLTQVPDDLP TNITVLNLTH NQLRRLPAAN FTRYSQLTSL DVGFNTISK LEPELCQKLP MLKVLNLQHN ELSQLSDKTF AFCTNLTELH LMSNSIQKIK NNPFVKQKNL ITLDLSHNGL S STKLGTQV QLENLQELLL SNNKIQALKS EELDIFANSS LKKLELSSNQ IKEFSPGCFH AIGRLFGLFL NNVQLGPSLT EK LCLELAN TSIRNLSLSN SQLSTTSNTT FLGLKWTNLT MLDLSYNNLN VVGNDSFAWL PQLEYFFLEY NNIQHLFSHS LHG LFNVRY LNLKRSFTKQ SISLASLPKI DDFSFQWLKC LEHLNMEDND IPGIKSNMFT GLINLKYLSL SNSFTSLRTL TNET FVSLA HSPLHILNLT KNKISKIESD AFSWLGHLEV LDLGLNEIGQ ELTGQEWRGL ENIFEIYLSY NKYLQLTRNS FALVP SLQR LMLRRVALKN VDSSPSPFQP LRNLTILDLS NNNIANINDD MLEGLEKLEI LDLQHNNLAR LWKHANPGGP IYFLKG LSH LHILNLESNG FDEIPVEVFK DLFELKIIDL GLNNLNTLPA SVFNNQVSLK SLNLQKNLIT SVEKKVFGPA FRNLTEL DM RFNPFDCTCE SIAWFVNWIN ETHTNIPELS SHYLCNTPPH YHGFPVRLFD TSSCKDSAPF ELFFMINTSI LLIFIFIV L LIHFEGWRIS FYWNVSVHRV LGFKEIDRQT EQFEYAAYII HAYKDKDWVW EHFSSMEKED QSLKFCLEER DFEAGVFEL EAIVNSIKRS RKIIFVITHH LLKDPLCKRF KVHHAVQQAI EQNLDSIILV FLEEIPDYKL NHALCLRRGM FKSHCILNWP VQKERIGAF RHKLQVALGS KNSVH

UniProtKB: Toll-like receptor 3

-
Macromolecule #2: Protein unc-93 homolog B1

MacromoleculeName: Protein unc-93 homolog B1 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 66.695969 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: 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

UniProtKB: Protein unc-93 homolog B1

-
Macromolecule #5: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 5 / Number of copies: 9 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 5.5
Details: 25 mM Hepes-NaOH, pH 7.5, 0.2 M NaCl, and 0.01% GDN
GridModel: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: OTHER / Imaging mode: BRIGHT FIELD
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

-
Image processing

Startup modelType of model: PDB ENTRY
PDB model - PDB ID:

1ziw

Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 134000
Initial angle assignmentType: ANGULAR RECONSTITUTION
Final angle assignmentType: ANGULAR RECONSTITUTION

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more