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- EMDB-27641: The structure of the interleukin 11 signalling complex, truncated... -
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Open data
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Basic information
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Title | The structure of the interleukin 11 signalling complex, truncated gp130 | |||||||||
![]() | The structure of the interleukin 11 signalling complex, truncated gp130 | |||||||||
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![]() | complex / IL-6 family cytokine / gp130 / glycoprotein 130 / glycoprotein / CYTOKINE | |||||||||
Function / homology | ![]() interleukin-11 receptor binding / oncostatin-M-mediated signaling pathway / ciliary neurotrophic factor receptor activity / negative regulation of interleukin-6-mediated signaling pathway / leukemia inhibitory factor signaling pathway / interleukin-27 receptor activity / oncostatin-M receptor complex / ciliary neurotrophic factor receptor binding / interleukin-11 receptor activity / interleukin-11 binding ...interleukin-11 receptor binding / oncostatin-M-mediated signaling pathway / ciliary neurotrophic factor receptor activity / negative regulation of interleukin-6-mediated signaling pathway / leukemia inhibitory factor signaling pathway / interleukin-27 receptor activity / oncostatin-M receptor complex / ciliary neurotrophic factor receptor binding / interleukin-11 receptor activity / interleukin-11 binding / interleukin-6 receptor activity / interleukin-6 binding / ciliary neurotrophic factor-mediated signaling pathway / ciliary neurotrophic factor receptor complex / interleukin-27-mediated signaling pathway / interleukin-6 receptor complex / head development / megakaryocyte differentiation / 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-mediated signaling pathway / Interleukin-6 signaling / positive regulation of Notch signaling pathway / protein tyrosine kinase activator activity / positive regulation of cardiac muscle hypertrophy / cytokine binding / 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 T cell proliferation / positive regulation of tyrosine phosphorylation of STAT protein / B cell differentiation / response to cytokine / cytokine activity / growth factor activity / cytokine-mediated signaling pathway / transmembrane signaling receptor activity / positive regulation of peptidyl-tyrosine phosphorylation / positive regulation of peptidyl-serine phosphorylation / scaffold protein binding / negative regulation of neuron apoptotic process / cell population proliferation / 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 / identical protein binding / membrane / plasma membrane / cytoplasm Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.47 Å | |||||||||
![]() | Metcalfe RD / Hanssen E / Griffin MDW | |||||||||
Funding support | ![]()
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![]() | ![]() 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 |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 48.6 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 19.5 KB 19.5 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 10.9 KB | Display | ![]() |
Images | ![]() | 115.5 KB | ||
Filedesc metadata | ![]() | 6.2 KB | ||
Others | ![]() ![]() | 38.8 MB 38.8 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 831.3 KB | Display | ![]() |
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Full document | ![]() | 830.9 KB | Display | |
Data in XML | ![]() | 14.3 KB | Display | |
Data in CIF | ![]() | 20.3 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8dpsMC ![]() 8dptC ![]() 8dpuC ![]() 8dpvC ![]() 8dpwC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | The structure of the interleukin 11 signalling complex, truncated gp130 | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.31 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: The structure of the interleukin 11 signalling complex,...
File | emd_27641_half_map_1.map | ||||||||||||
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Annotation | The structure of the interleukin 11 signalling complex, truncated gp130 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: The structure of the interleukin 11 signalling complex,...
File | emd_27641_half_map_2.map | ||||||||||||
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Annotation | The structure of the interleukin 11 signalling complex, truncated gp130 | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : Interleukin 11 signalling complex
Entire | Name: Interleukin 11 signalling complex |
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Components |
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-Supramolecule #1: Interleukin 11 signalling complex
Supramolecule | Name: Interleukin 11 signalling complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 / Details: 2:2:2 hexameric complex |
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Molecular weight | Theoretical: 182 KDa |
-Supramolecule #2: gp130
Supramolecule | Name: gp130 / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() |
-Supramolecule #3: Interleukin-11 receptor subunit alpha
Supramolecule | Name: Interleukin-11 receptor subunit alpha / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #3 |
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Source (natural) | Organism: ![]() |
-Supramolecule #4: Interleukin-11
Supramolecule | Name: Interleukin-11 / type: complex / ID: 4 / Parent: 1 / Macromolecule list: #2 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Interleukin-6 receptor subunit beta
Macromolecule | Name: Interleukin-6 receptor subunit beta / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 34.563961 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: 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 GITYED UniProtKB: Interleukin-6 receptor subunit beta |
-Macromolecule #2: Interleukin-11
Macromolecule | Name: Interleukin-11 / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 18.273289 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: 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
Macromolecule | Name: Interleukin-11 receptor subunit alpha / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 32.208002 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: 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
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 6 / Number of copies: 4 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 0.5 mg/mL | |||||||||
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Buffer | pH: 8.5 Component:
Details: TBS pH 85 | |||||||||
Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TALOS ARCTICA |
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Image recording | Film or detector model: GATAN K2 QUANTUM (4k x 4k) / Average electron dose: 52.0 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.8 µm |
Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |