[English] 日本語
Yorodumi
- EMDB-22098: Interleukin-10 signaling complex with IL-10RA and IL-10RB -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-22098
TitleInterleukin-10 signaling complex with IL-10RA and IL-10RB
Map dataSharpened map of the hexameric Interleukin-10 signaling complex with IL-10RA and IL-10RB
Sample
  • Complex: Interleukin-10 signaling complex with IL-10RA and IL-10RB
    • Complex: Interleukin-10, IL-10RA
      • Protein or peptide: Interleukin-10Interleukin 10
      • Protein or peptide: Interleukin-10 receptor subunit alpha
    • Complex: IL-10RB
      • Protein or peptide: Interleukin-10 receptor subunit beta
Function / homology
Function and homology information


interleukin-10 binding / negative regulation of chronic inflammatory response to antigenic stimulus / interleukin-10 receptor binding / regulation of response to wounding / interleukin-10 receptor activity / negative regulation of cytokine activity / interleukin-28 receptor complex / 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 binding / regulation of response to wounding / interleukin-10 receptor activity / negative regulation of cytokine activity / interleukin-28 receptor complex / 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 / negative regulation of heterotypic cell-cell adhesion / positive regulation of cellular respiration / 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 signaling receptor activity / positive regulation of heterotypic cell-cell adhesion / CD163 mediating an anti-inflammatory response / negative regulation of cytokine production / cellular response to hepatocyte growth factor stimulus / Other interleukin signaling / regulation of synapse organization / Interleukin-20 family signaling / positive regulation of sprouting angiogenesis / B cell proliferation / negative regulation of B cell proliferation / defense response to protozoan / Interleukin-10 signaling / negative regulation of vascular associated smooth muscle cell proliferation / negative regulation of interleukin-6 production / hemopoiesis / negative regulation of type II interferon production / positive regulation of immunoglobulin production / negative regulation of tumor necrosis factor production / negative regulation of mitotic cell cycle / positive regulation of cell cycle / response to glucocorticoid / negative regulation of T cell proliferation / positive regulation of vascular associated smooth muscle cell proliferation / Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation / positive regulation of endothelial cell proliferation / negative regulation of autophagy / B cell differentiation / FCGR3A-mediated IL10 synthesis / response to activity / cytokine activity / cellular response to estradiol stimulus / liver regeneration / positive regulation of cytokine production / 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 / negative regulation of inflammatory response / positive regulation of miRNA transcription / cytokine-mediated signaling pathway / positive regulation of DNA-binding transcription factor activity / 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 / immune response / response to xenobiotic stimulus / inflammatory 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)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.5 Å
AuthorsSaxton RA / Tsutsumi N / Gati C / Garcia KC
Funding support United States, 1 items
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, 2020-
Header (metadata) releaseMar 17, 2021-
Map releaseMar 17, 2021-
UpdateMar 31, 2021-
Current statusMar 31, 2021Processing site: RCSB / Status: Released

-
Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.4
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by cylindrical radius
  • Surface level: 0.4
  • Imaged by UCSF Chimera
  • Download
  • Surface view with fitted model
  • Atomic models: PDB-6x93
  • Surface level: 0.4
  • Imaged by UCSF Chimera
  • Download
  • Simplified surface model + fitted atomic model
  • Atomic modelsPDB-6x93
  • Imaged by Jmol
  • Download
Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_22098.png

Downloads & links

-
Map

FileDownload / File: emd_22098.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationSharpened map of the hexameric Interleukin-10 signaling complex with IL-10RA and IL-10RB
Voxel sizeX=Y=Z: 1.078 Å
Density
Contour LevelBy AUTHOR: 0.4 / Movie #1: 0.4
Minimum - Maximum-1.4334321 - 2.4508932
Average (Standard dev.)-8.663789e-05 (±0.047957122)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions256256256
Spacing256256256
CellA=B=C: 275.968 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.0781.0781.078
M x/y/z256256256
origin x/y/z0.0000.0000.000
length x/y/z275.968275.968275.968
α/β/γ90.00090.00090.000
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS256256256
D min/max/mean-1.4332.451-0.000

-
Supplemental data

-
Additional map: Unsharpened map of the hexameric Interleukin-10 signaling complex...

Fileemd_22098_additional_1.map
AnnotationUnsharpened map of the hexameric Interleukin-10 signaling complex with IL-10RA and IL-10RB
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Interleukin-10 signaling complex with IL-10RA and IL-10RB

EntireName: Interleukin-10 signaling complex with IL-10RA and IL-10RB
Components
  • Complex: Interleukin-10 signaling complex with IL-10RA and IL-10RB
    • Complex: Interleukin-10, IL-10RA
      • Protein or peptide: Interleukin-10Interleukin 10
      • Protein or peptide: Interleukin-10 receptor subunit alpha
    • Complex: IL-10RB
      • Protein or peptide: Interleukin-10 receptor subunit beta

-
Supramolecule #1: Interleukin-10 signaling complex with IL-10RA and IL-10RB

SupramoleculeName: Interleukin-10 signaling complex with IL-10RA and IL-10RB
type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Molecular weightTheoretical: 130 KDa

-
Supramolecule #2: Interleukin-10, IL-10RA

SupramoleculeName: Interleukin-10, IL-10RA / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1-#2
Source (natural)Organism: Homo sapiens (human)
Recombinant expressionOrganism: Homo sapiens (human)

-
Supramolecule #3: IL-10RB

SupramoleculeName: IL-10RB / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #3
Source (natural)Organism: Homo sapiens (human)
Recombinant expressionOrganism: Trichoplusia ni (cabbage looper)

-
Macromolecule #1: Interleukin-10

MacromoleculeName: Interleukin-10 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 18.778543 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
SPGQGTQSEN SCTHFPGYLP NMLRDLRDAF SRVKTFFQMK DQLDNLLLKE SLLEDFKGYL GCQALSEMIQ FYLEEVMPQA ENQDPDIKA HVQSLGENLK DLRLWLRRCH RFLPCENKSK AVEQVKNAFN KLQEKGIYKA MSEFDIFINY IEAYMTMKIR N

-
Macromolecule #2: Interleukin-10 receptor subunit alpha

MacromoleculeName: Interleukin-10 receptor subunit alpha / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 24.422391 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: HGTELPSPPS VWFEAEFFHH ILHWTPIPNQ SESTCYEVAL LRYGIESWNS ISNCSQTLSY DLTAVTLDLY HSNGYRARVR AVDGSRHSN WTVTNTRFSV DEVTLTVGSV NLEIHNGFIL GKIQLPRPKM APANDTYESI FSHFREYEIA IRKVPGNFTF T HKKVKHEN ...String:
HGTELPSPPS VWFEAEFFHH ILHWTPIPNQ SESTCYEVAL LRYGIESWNS ISNCSQTLSY DLTAVTLDLY HSNGYRARVR AVDGSRHSN WTVTNTRFSV DEVTLTVGSV NLEIHNGFIL GKIQLPRPKM APANDTYESI FSHFREYEIA IRKVPGNFTF T HKKVKHEN FSLLTSGEVG EFCVQVKPSV ASRSNKGMWS KEECISLTRQ YFTVTN

-
Macromolecule #3: Interleukin-10 receptor subunit beta

MacromoleculeName: Interleukin-10 receptor subunit beta / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 23.569334 KDa
Recombinant expressionOrganism: Trichoplusia ni (cabbage looper)
SequenceString: MVPPPENVRM NSVNFKNILQ WESPAFAKGQ LTFTAQYLSY RIFQDKCMQT TLTECDFSSL SKYGDHTLRV RAEFADEHSD WVQITFCPV DDTIIGPPGM QVEVLADSLH MRFLAPKIEN EYETWTMKNV YNSWTYNVQY WKNGTDEKFQ ITPQYDFEVL R NLEPWTTY ...String:
MVPPPENVRM NSVNFKNILQ WESPAFAKGQ LTFTAQYLSY RIFQDKCMQT TLTECDFSSL SKYGDHTLRV RAEFADEHSD WVQITFCPV DDTIIGPPGM QVEVLADSLH MRFLAPKIEN EYETWTMKNV YNSWTYNVQY WKNGTDEKFQ ITPQYDFEVL R NLEPWTTY CVQVRGFLPD RNKAGEWSEP VCEQTTHDET VPS

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

Concentration10 mg/mL
BufferpH: 7.2
Component:
ConcentrationName
10.0 mMHEPES
150.0 mMSodium chloride
0.001 % (w/v)GDN
0.0001 % (w/v)CHS
0.05 % (w/v)Digitonin
GridModel: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Pretreatment - Type: GLOW DISCHARGE
VitrificationCryogen name: ETHANE / Chamber humidity: 95 % / Chamber temperature: 293 K / Instrument: LEICA EM GP / Details: 5s blotting.

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsC2 aperture diameter: 100.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Cs: 2.7 mm / Nominal defocus max: -2.0 µm / Nominal defocus min: -0.8 µm / Nominal magnification: 81000
Specialist opticsEnergy filter - Name: GIF Bioquantum / Energy filter - Slit width: 20 eV
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Number grids imaged: 1 / Number real images: 9413 / Average electron dose: 50.0 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

-
Image processing

Particle selectionNumber selected: 6701298
CTF correctionSoftware - Name: cryoSPARC
Startup modelType of model: OTHER / Details: Initial model generation in cryoSPARC.
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC
Final reconstructionApplied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 86725

-
Atomic model buiding 1

Initial model(PDB ID:

1y6k

,

3lqm

)
RefinementSpace: REAL / Protocol: FLEXIBLE FIT
Output model

PDB-6x93:
Interleukin-10 signaling complex with IL-10RA and IL-10RB

+
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