[English] 日本語
Yorodumi
- EMDB-27642: The structure of the IL-11 signalling complex, with full-length e... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-27642
TitleThe structure of the IL-11 signalling complex, with full-length extracellular gp130
Map dataThe structure of the IL-11 signalling complex, with full-length extracellular gp130
Sample
  • Complex: Interleukin 11 signalling complex
    • Complex: gp130
      • Protein or peptide: Interleukin-6 receptor subunit beta
    • Complex: IL-11Ra
      • Protein or peptide: Interleukin-11 receptor subunit alpha
    • Complex: IL-11
      • Protein or peptide: Interleukin-11Interleukin 11
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
KeywordsComplex / GP130 / glycoprotein 130 / signalling / cancer / CYTOKINE
Function / homology
Function and homology information


interleukin-11 receptor binding / interleukin-27 receptor activity / oncostatin-M receptor complex / oncostatin-M-mediated signaling pathway / ciliary neurotrophic factor receptor activity / ciliary neurotrophic factor receptor binding / negative regulation of interleukin-6-mediated signaling pathway / leukemia inhibitory factor signaling pathway / interleukin-11 receptor activity / interleukin-11 binding ...interleukin-11 receptor binding / interleukin-27 receptor activity / oncostatin-M receptor complex / oncostatin-M-mediated signaling pathway / ciliary neurotrophic factor receptor activity / ciliary neurotrophic factor receptor binding / negative regulation of interleukin-6-mediated signaling pathway / leukemia inhibitory factor signaling pathway / interleukin-11 receptor activity / interleukin-11 binding / megakaryocyte differentiation / ciliary neurotrophic factor receptor complex / interleukin-27-mediated signaling pathway / ciliary neurotrophic factor-mediated signaling pathway / interleukin-6 receptor complex / head development / negative regulation of hormone secretion / interleukin-11-mediated signaling pathway / T-helper 17 cell lineage commitment / positive regulation of adaptive immune response / developmental process / positive regulation of acute inflammatory response / positive regulation of astrocyte differentiation / intestinal epithelial cell development / positive regulation of platelet aggregation / Interleukin-35 Signalling / Interleukin-27 signaling / IL-6-type cytokine receptor ligand interactions / cytokine receptor activity / glycogen metabolic process / Interleukin-6 signaling / interleukin-6-mediated signaling pathway / positive regulation of Notch signaling pathway / protein tyrosine kinase activator activity / cytokine binding / positive regulation of cardiac muscle hypertrophy / fat cell differentiation / MAPK3 (ERK1) activation / growth factor binding / MAPK1 (ERK2) activation / positive regulation of vascular endothelial growth factor production / positive regulation of osteoblast differentiation / coreceptor activity / positive regulation of tyrosine phosphorylation of STAT protein / positive regulation of T cell proliferation / B cell differentiation / response to cytokine / cytokine activity / growth factor activity / cytokine-mediated signaling pathway / positive regulation of peptidyl-tyrosine phosphorylation / transmembrane signaling receptor activity / positive regulation of peptidyl-serine phosphorylation / scaffold protein binding / cell population proliferation / negative regulation of neuron apoptotic process / positive regulation of MAPK cascade / receptor complex / membrane raft / external side of plasma membrane / neuronal cell body / dendrite / positive regulation of cell population proliferation / negative regulation of apoptotic process / positive regulation of transcription by RNA polymerase II / extracellular space / extracellular exosome / extracellular region / membrane / identical protein binding / plasma membrane / cytoplasm
Similarity search - Function
Interleukin-11, mammalian / Interleukin-11 / Interleukin 11 / Type I cytokine receptor, cytokine-binding domain / Interleukin-6 receptor alpha chain, binding / Immunoglobulin C2-set-like, ligand-binding / Ig-like C2-type domain / Long hematopoietin receptor, soluble alpha chain, conserved site / Long hematopoietin receptor, soluble alpha chains family signature. / Long hematopoietin receptor, Gp130 family 2, conserved site ...Interleukin-11, mammalian / Interleukin-11 / Interleukin 11 / Type I cytokine receptor, cytokine-binding domain / Interleukin-6 receptor alpha chain, binding / Immunoglobulin C2-set-like, ligand-binding / Ig-like C2-type domain / Long hematopoietin receptor, soluble alpha chain, conserved site / Long hematopoietin receptor, soluble alpha chains family signature. / Long hematopoietin receptor, Gp130 family 2, conserved site / Long hematopoietin receptor, gp130 family signature. / Four-helical cytokine-like, core / Fibronectin type III domain / Fibronectin type 3 domain / Fibronectin type-III domain profile. / Fibronectin type III / Fibronectin type III superfamily / Immunoglobulin subtype / Immunoglobulin / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / Immunoglobulin-like fold
Similarity search - Domain/homology
Interleukin-11 / Interleukin-6 receptor subunit beta / Interleukin-11 receptor subunit alpha
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 4.0 Å
AuthorsMetcalfe RD / Hanssen E / Griffin MDW
Funding support Australia, 1 items
OrganizationGrant numberCountry
National Health and Medical Research Council (NHMRC, Australia)APP1147621 Australia
CitationJournal: Nat Commun / Year: 2023
Title: Structures of the interleukin 11 signalling complex reveal gp130 dynamics and the inhibitory mechanism of a cytokine variant.
Authors: Riley D Metcalfe / Eric Hanssen / Ka Yee Fung / Kaheina Aizel / Clara C Kosasih / Courtney O Zlatic / Larissa Doughty / Craig J Morton / Andrew P Leis / Michael W Parker / Paul R Gooley / ...Authors: Riley D Metcalfe / Eric Hanssen / Ka Yee Fung / Kaheina Aizel / Clara C Kosasih / Courtney O Zlatic / Larissa Doughty / Craig J Morton / Andrew P Leis / Michael W Parker / Paul R Gooley / Tracy L Putoczki / Michael D W Griffin /
Abstract: Interleukin (IL-)11, an IL-6 family cytokine, has pivotal roles in autoimmune diseases, fibrotic complications, and solid cancers. Despite intense therapeutic targeting efforts, structural ...Interleukin (IL-)11, an IL-6 family cytokine, has pivotal roles in autoimmune diseases, fibrotic complications, and solid cancers. Despite intense therapeutic targeting efforts, structural understanding of IL-11 signalling and mechanistic insights into current inhibitors are lacking. Here we present cryo-EM and crystal structures of the human IL-11 signalling complex, including the complex containing the complete extracellular domains of the shared IL-6 family β-receptor, gp130. We show that complex formation requires conformational reorganisation of IL-11 and that the membrane-proximal domains of gp130 are dynamic. We demonstrate that the cytokine mutant, IL-11 Mutein, competitively inhibits signalling in human cell lines. Structural shifts in IL-11 Mutein underlie inhibition by altering cytokine binding interactions at all three receptor-engaging sites and abrogating the final gp130 binding step. Our results reveal the structural basis of IL-11 signalling, define the molecular mechanisms of an inhibitor, and advance understanding of gp130-containing receptor complexes, with potential applications in therapeutic development.
History
DepositionJul 17, 2022-
Header (metadata) releaseNov 29, 2023-
Map releaseNov 29, 2023-
UpdateMay 1, 2024-
Current statusMay 1, 2024Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

emd_27642.png

Downloads & links

-
Map

FileDownload / File: emd_27642.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationThe structure of the IL-11 signalling complex, with full-length extracellular gp130
Voxel sizeX=Y=Z: 1.31 Å
Density
Contour LevelBy AUTHOR: 3.0
Minimum - Maximum-40.695369999999997 - 60.532769999999999
Average (Standard dev.)-0.000000000002256 (±1.0)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderZYX
Origin000
Dimensions300300300
Spacing300300300
CellA=B=C: 392.99997 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: The structure of the IL-11 signalling complex, with...

Fileemd_27642_half_map_1.map
AnnotationThe structure of the IL-11 signalling complex, with full-length extracellular gp130
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: The structure of the IL-11 signalling complex, with...

Fileemd_27642_half_map_2.map
AnnotationThe structure of the IL-11 signalling complex, with full-length extracellular gp130
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Interleukin 11 signalling complex

EntireName: Interleukin 11 signalling complex
Components
  • Complex: Interleukin 11 signalling complex
    • Complex: gp130
      • Protein or peptide: Interleukin-6 receptor subunit beta
    • Complex: IL-11Ra
      • Protein or peptide: Interleukin-11 receptor subunit alpha
    • Complex: IL-11
      • Protein or peptide: Interleukin-11Interleukin 11
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

-
Supramolecule #1: Interleukin 11 signalling complex

SupramoleculeName: Interleukin 11 signalling complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3
Details: 2:2:2 hexameric complex of IL-11, IL-11Ra and gp130. Purified from recombinantly expressed and purified proteins.
Molecular weightTheoretical: 290 KDa

-
Supramolecule #2: gp130

SupramoleculeName: gp130 / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1
Source (natural)Organism: Homo sapiens (human)

-
Supramolecule #3: IL-11Ra

SupramoleculeName: IL-11Ra / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #3
Source (natural)Organism: Homo sapiens (human)

-
Supramolecule #4: IL-11

SupramoleculeName: IL-11 / type: complex / ID: 4 / Parent: 1 / Macromolecule list: #2
Source (natural)Organism: Homo sapiens (human)

-
Macromolecule #1: Interleukin-6 receptor subunit beta

MacromoleculeName: Interleukin-6 receptor subunit beta / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 67.199836 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: GELLDPCGYI SPESPVVQLH SNFTAVCVLK EKCMDYFHVN ANYIVWKTNH FTIPKEQYTI INRTASSVTF TDIASLNIQL TCNILTFGQ LEQNVYGITI ISGLPPEKPK NLSCIVNEGK KMRCEWDGGR ETHLETNFTL KSEWATHKFA DCKAKRDTPT S CTVDYSTV ...String:
GELLDPCGYI SPESPVVQLH SNFTAVCVLK EKCMDYFHVN ANYIVWKTNH FTIPKEQYTI INRTASSVTF TDIASLNIQL TCNILTFGQ LEQNVYGITI ISGLPPEKPK NLSCIVNEGK KMRCEWDGGR ETHLETNFTL KSEWATHKFA DCKAKRDTPT S CTVDYSTV YFVNIEVWVE AENALGKVTS DHINFDPVYK VKPNPPHNLS VINSEELSSI LKLTWTNPSI KSVIILKYNI QY RTKDAST WSQIPPEDTA STRSSFTVQD LKPFTEYVFR IRCMKEDGKG YWSDWSEEAS GITYEDRPSK APSFWYKIDP SHT QGYRTV QLVWKTLPPF EANGKILDYE VTLTRWKSHL QNYTVNATKL TVNLTNDRYL ATLTVRNLVG KSDAAVLTIP ACDF QATHP VMDLKAFPKD NMLWVEWTTP RESVKKYILE WCVLSDKAPC ITDWQQEDGT VHRTYLRGNL AESKCYLITV TPVYA DGPG SPESIKAYLK QAPPSKGPTV RTKKVGKNEA VLEWDQLPVD VQNGFIRNYT IFYRTIIGNE TAVNVDSSHT EYTLSS LTS DTLYMVRMAA YTDEGGKDGP EFTFTTPK

UniProtKB: Interleukin-6 receptor subunit beta

-
Macromolecule #2: Interleukin-11

MacromoleculeName: Interleukin-11 / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 18.273289 KDa
Recombinant expressionOrganism: Escherichia coli BL21 (bacteria)
SequenceString:
GSPDPRAELD STVLLTRSLL ADTRQLAAQL RDKFPADGDH NLDSLPTLAM SAGALGALQL PGVLTRLRAD LLSYLRHVQW LRRAGGSSL KTLEPELGTL QARLDRLLRR LQLLMSRLAL PQPPPDPPAP PLAPPSSAWG GIRAAHAILG GLHLTLDWAV R GLLLLKTR L

UniProtKB: Interleukin-11

-
Macromolecule #3: Interleukin-11 receptor subunit alpha

MacromoleculeName: Interleukin-11 receptor subunit alpha / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 32.208002 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: GSSPCPQAWG PPGVQYGQPG RSVKLCCPGV TAGDPVSWFR DGEPKLLQGP DSGLGHELVL AQADSTDEGT YICQTLDGAL GGTVTLQLG YPPARPVVSC QAADYENFSC TWSPSQISGL PTRYLTSYRK KTVLGADSQR RSPSTGPWPC PQDPLGAARC V VHGAEFWS ...String:
GSSPCPQAWG PPGVQYGQPG RSVKLCCPGV TAGDPVSWFR DGEPKLLQGP DSGLGHELVL AQADSTDEGT YICQTLDGAL GGTVTLQLG YPPARPVVSC QAADYENFSC TWSPSQISGL PTRYLTSYRK KTVLGADSQR RSPSTGPWPC PQDPLGAARC V VHGAEFWS QYRINVTEVN PLGASTRLLD VSLQSILRPD PPQGLRVESV PGYPRRLRAS WTYPASWPSQ PHFLLKFRLQ YR PAQHPAW STVEPAGLEE VITDAVAGLP HAVRVSARDF LDAGTWSTWS PEAWGTPSTG T

UniProtKB: Interleukin-11 receptor subunit alpha

-
Macromolecule #6: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 6 / Number of copies: 4 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 8.5
GridModel: Quantifoil R1.2/1.3 / Material: GOLD
VitrificationCryogen name: ETHANE / Chamber humidity: 95 % / Chamber temperature: 295 K / Instrument: FEI VITROBOT MARK IV

-
Electron microscopy

MicroscopeFEI TECNAI ARCTICA
Electron beamAcceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination 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
Image recordingFilm or detector model: GATAN K2 QUANTUM (4k x 4k) / Average electron dose: 52.0 e/Å2
Experimental equipment
Model: Talos Arctica / Image courtesy: FEI Company

-
Image processing

Startup modelType of model: NONE
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
Final reconstructionApplied symmetry - Point group: C2 (2 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 4.0 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 125373
FSC plot (resolution estimation)

+
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