[English] 日本語
Yorodumi
- PDB-6x93: Interleukin-10 signaling complex with IL-10RA and IL-10RB -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6x93
TitleInterleukin-10 signaling complex with IL-10RA and IL-10RB
Components
  • Interleukin-10 receptor subunit alpha
  • Interleukin-10 receptor subunit beta
  • Interleukin-10Interleukin 10
KeywordsCYTOKINE / IL-10 / receptor / IL-10RA / IL-10RB / signaling
Function / homology
Function and homology information


interleukin-10 binding / negative regulation of chronic inflammatory response to antigenic stimulus / interleukin-10 receptor activity / interleukin-10 receptor binding / regulation of response to wounding / interleukin-28 receptor complex / negative regulation of cytokine activity / negative regulation of interleukin-18 production / negative regulation of myeloid dendritic cell activation / negative regulation of interferon-alpha production ...interleukin-10 binding / negative regulation of chronic inflammatory response to antigenic stimulus / interleukin-10 receptor activity / interleukin-10 receptor binding / regulation of response to wounding / interleukin-28 receptor complex / negative regulation of cytokine activity / negative regulation of interleukin-18 production / negative regulation of myeloid dendritic cell activation / negative regulation of interferon-alpha production / negative regulation of chemokine (C-C motif) ligand 5 production / response to carbon monoxide / positive regulation of plasma cell differentiation / positive regulation of B cell apoptotic process / ubiquitin-dependent endocytosis / response to inactivity / chronic inflammatory response to antigenic stimulus / cytoplasmic sequestering of NF-kappaB / intestinal epithelial structure maintenance / negative regulation of membrane protein ectodomain proteolysis / regulation of isotype switching / positive regulation of cellular respiration / negative regulation of heterotypic cell-cell adhesion / negative regulation of cytokine production involved in immune response / type III interferon-mediated signaling pathway / negative regulation of interleukin-1 production / negative regulation of MHC class II biosynthetic process / branching involved in labyrinthine layer morphogenesis / negative regulation of interleukin-8 production / negative regulation of nitric oxide biosynthetic process / negative regulation of interleukin-12 production / negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway / type 2 immune response / endothelial cell apoptotic process / positive regulation of macrophage activation / positive regulation of MHC class II biosynthetic process / leukocyte chemotaxis / positive regulation of heterotypic cell-cell adhesion / positive regulation of signaling receptor activity / negative regulation of cytokine production / CD163 mediating an anti-inflammatory response / positive regulation of immunoglobulin production / Other interleukin signaling / cellular response to hepatocyte growth factor stimulus / Interleukin-20 family signaling / regulation of synapse organization / positive regulation of sprouting angiogenesis / B cell proliferation / negative regulation of B cell proliferation / defense response to protozoan / negative regulation of vascular associated smooth muscle cell proliferation / Interleukin-10 signaling / negative regulation of interleukin-6 production / hemopoiesis / negative regulation of type II interferon production / negative regulation of tumor necrosis factor production / negative regulation of mitotic cell cycle / positive regulation of cell cycle / negative regulation of T cell proliferation / response to glucocorticoid / positive regulation of vascular associated smooth muscle cell proliferation / positive regulation of endothelial cell proliferation / Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation / B cell differentiation / negative regulation of autophagy / FCGR3A-mediated IL10 synthesis / response to activity / positive regulation of cytokine production / cytokine activity / cellular response to estradiol stimulus / liver regeneration / positive regulation of receptor signaling pathway via JAK-STAT / growth factor activity / response to insulin / response to molecule of bacterial origin / cellular response to virus / positive regulation of DNA-binding transcription factor activity / cytokine-mediated signaling pathway / negative regulation of inflammatory response / positive regulation of miRNA transcription / signaling receptor activity / regulation of gene expression / Interleukin-4 and Interleukin-13 signaling / defense response to virus / cellular response to lipopolysaccharide / response to lipopolysaccharide / protein dimerization activity / defense response to bacterium / response to xenobiotic stimulus / inflammatory response / immune response / apical plasma membrane / negative regulation of cell population proliferation / negative regulation of apoptotic process / positive regulation of DNA-templated transcription / signal transduction / positive regulation of transcription by RNA polymerase II / extracellular space / extracellular region / membrane
Similarity search - Function
Interleukin-10 / Interleukin-10 family / Interleukin-10/19/20/22/24/26 family / Interleukin 10 / Interleukin-10, conserved site / Interleukin-10 family signature. / Interferon/interleukin receptor domain / Interferon-alpha/beta receptor, fibronectin type III / Tissue factor / Four-helical cytokine-like, core ...Interleukin-10 / Interleukin-10 family / Interleukin-10/19/20/22/24/26 family / Interleukin 10 / Interleukin-10, conserved site / Interleukin-10 family signature. / Interferon/interleukin receptor domain / Interferon-alpha/beta receptor, fibronectin type III / Tissue factor / Four-helical cytokine-like, core / Fibronectin type-III domain profile. / Fibronectin type III / Fibronectin type III superfamily / Immunoglobulin-like fold
Similarity search - Domain/homology
Interleukin-10 / Interleukin-10 receptor subunit beta / Interleukin-10 receptor subunit alpha
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.5 Å
AuthorsSaxton, R.A. / Tsutsumi, N. / Gati, C. / Garcia, K.C.
Funding support United States, 1items
OrganizationGrant numberCountry
Department of Energy (DOE, United States)DE-AC02-76SF00515 United States
CitationJournal: Science / Year: 2021
Title: Structure-based decoupling of the pro- and anti-inflammatory functions of interleukin-10.
Authors: Robert A Saxton / Naotaka Tsutsumi / Leon L Su / Gita C Abhiraman / Kritika Mohan / Lukas T Henneberg / Nanda G Aduri / Cornelius Gati / K Christopher Garcia /
Abstract: Interleukin-10 (IL-10) is an immunoregulatory cytokine with both anti-inflammatory and immunostimulatory properties and is frequently dysregulated in disease. We used a structure-based approach to ...Interleukin-10 (IL-10) is an immunoregulatory cytokine with both anti-inflammatory and immunostimulatory properties and is frequently dysregulated in disease. We used a structure-based approach to deconvolute IL-10 pleiotropy by determining the structure of the IL-10 receptor (IL-10R) complex by cryo-electron microscopy at a resolution of 3.5 angstroms. The hexameric structure shows how IL-10 and IL-10Rα form a composite surface to engage the shared signaling receptor IL-10Rβ, enabling the design of partial agonists. IL-10 variants with a range of IL-10Rβ binding strengths uncovered substantial differences in response thresholds across immune cell populations, providing a means of manipulating IL-10 cell type selectivity. Some variants displayed myeloid-biased activity by suppressing macrophage activation without stimulating inflammatory CD8 T cells, thereby uncoupling the major opposing functions of IL-10. These results provide a mechanistic blueprint for tuning the pleiotropic actions of IL-10.
History
DepositionJun 2, 2020Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 17, 2021Provider: repository / Type: Initial release
Revision 1.1Mar 31, 2021Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.pdbx_database_id_PubMed ..._citation.journal_volume / _citation.pdbx_database_id_PubMed / _citation.title / _citation_author.identifier_ORCID

-
Structure visualization

Movie
  • Deposited structure unit
  • Imaged by Jmol
  • Download
  • Simplified surface model + fitted atomic model
  • EMDB-22098
  • Imaged by Jmol
  • Download
  • Superimposition on EM map
  • EMDB-22098
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Interleukin-10
B: Interleukin-10 receptor subunit alpha
C: Interleukin-10 receptor subunit beta
D: Interleukin-10
E: Interleukin-10 receptor subunit alpha
F: Interleukin-10 receptor subunit beta


Theoretical massNumber of molelcules
Total (without water)133,5416
Polymers133,5416
Non-polymers00
Water0
1


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

-
Components

#1: Protein Interleukin-10 / Interleukin 10 / IL-10 / Cytokine synthesis inhibitory factor / CSIF


Mass: 18778.543 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: IL10 / Production host: Homo sapiens (human) / References: UniProt: P22301
#2: Protein Interleukin-10 receptor subunit alpha / / IL-10RA / CDw210a / Interleukin-10 receptor subunit 1 / IL-10R1


Mass: 24422.391 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: IL10RA, IL10R / Production host: Homo sapiens (human) / References: UniProt: Q13651
#3: Protein Interleukin-10 receptor subunit beta / / IL-10RB / Cytokine receptor class-II member 4 / Cytokine receptor family 2 member 4 / CRF2-4 / ...IL-10RB / Cytokine receptor class-II member 4 / Cytokine receptor family 2 member 4 / CRF2-4 / Interleukin-10 receptor subunit 2 / IL-10R2


Mass: 23569.334 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: IL10RB, CRFB4, D21S58, D21S66 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q08334

-
Experimental details

-
Experiment

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

-
Sample preparation

Component
IDNameTypeEntity IDParent-IDSource
1Interleukin-10 signaling complex with IL-10RA and IL-10RBCOMPLEXall0MULTIPLE SOURCES
2Interleukin-10, IL-10RACOMPLEX#1-#21RECOMBINANT
3IL-10RBCOMPLEX#31RECOMBINANT
Molecular weightValue: 0.13 MDa / Experimental value: NO
Source (natural)
IDEntity assembly-IDOrganismNcbi tax-ID
12Homo sapiens (human)9606
23Homo sapiens (human)9606
Source (recombinant)
IDEntity assembly-IDOrganismNcbi tax-ID
12Homo sapiens (human)9606
23Trichoplusia ni (cabbage looper)7111
Buffer solutionpH: 7.2
Buffer component
IDConc.NameBuffer-ID
110 mMHEPES1
2150 mMSodium chloride1
30.001 % (w/v)GDN1
40.0001 % (w/v)CHS1
50.05 % (w/v)Digitonin1
SpecimenConc.: 10 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Specimen supportGrid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3
VitrificationInstrument: LEICA EM GP / Cryogen name: ETHANE / Humidity: 95 % / Chamber temperature: 293 K / Details: 5s blotting

-
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: FLOOD BEAM
Electron lensMode: BRIGHT FIELDBright-field microscopy / Nominal magnification: 81000 X / Nominal defocus max: -2000 nm / Nominal defocus min: -800 nm / Cs: 2.7 mm / C2 aperture diameter: 100 µm / Alignment procedure: COMA FREE
Specimen holderCryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER
Image recordingElectron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) / Num. of grids imaged: 1 / Num. of real images: 9413
EM imaging opticsEnergyfilter name: GIF Bioquantum / Energyfilter slit width: 20 eV

-
Processing

Software
NameVersionClassification
phenix.real_space_refine1.17.1_3660refinement
PHENIX1.17.1_3660refinement
EM software
IDNameCategory
1cryoSPARCparticle selection
2SerialEMimage acquisition
4cryoSPARCCTF correction
7PHENIXmodel fitting
9cryoSPARCinitial Euler assignment
10cryoSPARCfinal Euler assignment
11cryoSPARCclassification
12cryoSPARC3D reconstruction
19PHENIXmodel refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Particle selectionNum. of particles selected: 6701298
SymmetryPoint symmetry: C1 (asymmetric)
3D reconstructionResolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 86725 / Symmetry type: POINT
Atomic model buildingProtocol: FLEXIBLE FIT / Space: REAL
Atomic model building
IDPDB-ID 3D fitting-ID
11Y6K

1y6k

1
23LQM

3lqm

1
RefinementCross valid method: NONE
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
Displacement parametersBiso mean: 76.12 Å2
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00746951
ELECTRON MICROSCOPYf_angle_d1.12879517
ELECTRON MICROSCOPYf_chiral_restr0.05761140
ELECTRON MICROSCOPYf_plane_restr0.00691273
ELECTRON MICROSCOPYf_dihedral_angle_d19.61742116

+
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