[English] 日本語
Yorodumi
- PDB-7c77: Cryo-EM structure of mouse TLR3 in complex with UNC93B1 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7c77
TitleCryo-EM structure of mouse TLR3 in complex with UNC93B1
Components
  • Protein unc-93 homolog B1
  • Toll-like receptor 3
KeywordsIMMUNE SYSTEM / Toll-like receptors / UNC93B1 / MFS
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 / 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 ...Trafficking and processing of endosomal TLR / type III interferon production / positive regulation of type III interferon production / response to dsRNA / 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 / pattern recognition receptor activity / toll-like receptor signaling pathway / cellular response to exogenous dsRNA / response to exogenous dsRNA / antigen processing and presentation / positive regulation of type I interferon production / cellular response to interferon-beta / positive regulation of interferon-alpha production / extrinsic apoptotic signaling pathway / positive regulation of chemokine production / JNK cascade / positive regulation of interleukin-12 production / positive regulation of interferon-beta production / positive regulation of interleukin-8 production / positive regulation of JNK cascade / intracellular protein transport / microglial cell activation / response to virus / cell morphogenesis / cellular response to virus / defense response / cellular response to type II interferon / positive regulation of non-canonical NF-kappaB signal transduction / cellular response to mechanical stimulus / transmembrane signaling receptor activity / positive regulation of angiogenesis / antigen processing and presentation of exogenous peptide antigen via MHC class II / male gonad development / positive regulation of interleukin-6 production / positive regulation of tumor necrosis factor production / MAPK cascade / positive regulation of type II interferon production / double-stranded RNA binding / cellular response to xenobiotic stimulus / signaling receptor activity / positive regulation of canonical NF-kappaB signal transduction / defense response to virus / adaptive immune response / membrane => GO:0016020 / 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
Ion channel regulatory protein, UNC-93 / Ion channel regulatory protein UNC-93 / Protein unc-93 homolog B1 / Toll-like receptor 3 trans-membrane domain / Toll-like receptor 3 trans-membrane domain / Toll-like receptor / TIR domain / Leucine Rich Repeat / Cysteine-rich flanking region, C-terminal / Leucine rich repeat C-terminal domain ...Ion channel regulatory protein, UNC-93 / Ion channel regulatory protein UNC-93 / Protein unc-93 homolog B1 / Toll-like receptor 3 trans-membrane domain / Toll-like receptor 3 trans-membrane domain / Toll-like receptor / TIR domain / Leucine Rich Repeat / Cysteine-rich flanking region, C-terminal / Leucine rich repeat C-terminal domain / Toll - interleukin 1 - resistance / Leucine-rich repeat, SDS22-like subfamily / TIR domain profile. / 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
Protein unc-93 homolog B1 / Toll-like receptor 3
Similarity search - Component
Biological speciesMus musculus (house mouse)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å
AuthorsOhto, U. / Ishida, H. / Shimizu, T.
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, 2020Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Jan 6, 2021Provider: repository / Type: Initial release
Revision 1.1Jan 27, 2021Group: Database references / Category: citation / Item: _citation.pdbx_database_id_PubMed / _citation.title
Revision 1.2Feb 24, 2021Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first / _citation.page_last

-
Structure visualization

Movie
  • Deposited structure unit
  • Imaged by Jmol
  • Download
  • Superimposition on EM map
  • EMDB-30294
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Toll-like receptor 3
B: Protein unc-93 homolog B1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)175,10016
Polymers170,8252
Non-polymers4,27514
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_5551

-
Components

#1: Protein Toll-like receptor 3


Mass: 103785.797 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Gene: Tlr3 / Cell line (production host): Expi293F / Production host: Homo sapiens (human) / References: UniProt: Q99MB1
#2: Protein Protein unc-93 homolog B1 / Unc-93B1


Mass: 67039.250 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Gene: Unc93b1, Unc93b / Cell line (production host): Expi293F / Production host: Homo sapiens (human) / References: UniProt: Q8VCW4
#3: Polysaccharide beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 586.542 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DManpb1-4DGlcpNAcb1-4DGlcpNAcb1-Glycam Condensed SequenceGMML 1.0
WURCS=2.0/2,3,2/[a2122h-1b_1-5_2*NCC/3=O][a1122h-1b_1-5]/1-1-2/a4-b1_b4-c1WURCSPDB2Glycan 1.1.0
[]{[(4+1)][b-D-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{[(4+1)][b-D-Manp]{}}}}LINUCSPDB-CARE
#4: Polysaccharide
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 424.401 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DGlcpNAcb1-4DGlcpNAcb1-Glycam Condensed SequenceGMML 1.0
WURCS=2.0/1,2,1/[a2122h-1b_1-5_2*NCC/3=O]/1-1/a4-b1WURCSPDB2Glycan 1.1.0
[]{[(4+1)][b-D-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{}}}LINUCSPDB-CARE
#5: Sugar
ChemComp-NAG / 2-acetamido-2-deoxy-beta-D-glucopyranose / N-acetyl-beta-D-glucosamine / 2-acetamido-2-deoxy-beta-D-glucose / 2-acetamido-2-deoxy-D-glucose / 2-acetamido-2-deoxy-glucose / N-ACETYL-D-GLUCOSAMINE


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 9
Source method: isolated from a genetically manipulated source
Formula: C8H15NO6
IdentifierTypeProgram
DGlcpNAcbCONDENSED IUPAC CARBOHYDRATE SYMBOLGMML 1.0
N-acetyl-b-D-glucopyranosamineCOMMON NAMEGMML 1.0
b-D-GlcpNAcIUPAC CARBOHYDRATE SYMBOLPDB-CARE 1.0
GlcNAcSNFG CARBOHYDRATE SYMBOLGMML 1.0
Has ligand of interestN

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

ComponentName: Complex of TLR3 and UNC93B1 / Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT
Source (natural)Organism: Mus musculoides (Temminck's mouse)
Source (recombinant)Organism: Homo sapiens (human) / Cell: Expi293F
Buffer solutionpH: 7.5
Details: 25 mM Hepes-NaOH, pH 7.5, 0.2 M NaCl, and 0.01% GDN
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: OTHER
Electron lensMode: BRIGHT FIELD
Image recordingElectron dose: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

-
Processing

CTF correctionType: NONE
3D reconstructionResolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 72000 / Symmetry type: POINT

+
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://pdbjlvh1.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