+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-26382 | |||||||||
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Title | IL-27 quaternary receptor signaling complex | |||||||||
Map data | Sharpened Map | |||||||||
Sample |
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Function / homology | Function and homology information interleukin-27 receptor binding / regulation of T-helper 1 cell differentiation / negative regulation of T cell extravasation / negative regulation of T-helper 17 type immune response / oncostatin-M-mediated signaling pathway / interleukin-27 receptor activity / ciliary neurotrophic factor receptor activity / negative regulation of interleukin-6-mediated signaling pathway / leukemia inhibitory factor signaling pathway / negative regulation of type 2 immune response ...interleukin-27 receptor binding / regulation of T-helper 1 cell differentiation / negative regulation of T cell extravasation / negative regulation of T-helper 17 type immune response / oncostatin-M-mediated signaling pathway / interleukin-27 receptor activity / ciliary neurotrophic factor receptor activity / negative regulation of interleukin-6-mediated signaling pathway / leukemia inhibitory factor signaling pathway / negative regulation of type 2 immune response / oncostatin-M receptor complex / regulation of isotype switching to IgG isotypes / ciliary neurotrophic factor receptor binding / interleukin-11 receptor activity / interleukin-11 binding / ciliary neurotrophic factor-mediated signaling pathway / ciliary neurotrophic factor receptor complex / interleukin-27-mediated signaling pathway / interleukin-6 receptor complex / response to Gram-positive bacterium / interleukin-11-mediated signaling pathway / positive regulation of T-helper 1 type immune response / T-helper 17 cell lineage commitment / positive regulation of adaptive immune response / positive regulation of alpha-beta T cell proliferation / positive regulation of acute inflammatory response / protein tyrosine kinase activator activity / positive regulation of astrocyte differentiation / intestinal epithelial cell development / positive regulation of platelet aggregation / negative regulation of interleukin-17 production / Interleukin-27 signaling / IL-6-type cytokine receptor ligand interactions / Interleukin-35 Signalling / cytokine receptor activity / T-helper 1 type immune response / glycogen metabolic process / interleukin-6-mediated signaling pathway / Interleukin-6 signaling / regulation of T cell proliferation / positive regulation of Notch signaling pathway / positive regulation of cardiac muscle hypertrophy / MAPK3 (ERK1) activation / growth factor binding / cytokine binding / MAPK1 (ERK2) activation / negative regulation of interleukin-6 production / humoral immune response / negative regulation of tumor necrosis factor production / positive regulation of vascular endothelial growth factor production / positive regulation of osteoblast differentiation / coreceptor activity / T cell proliferation / positive regulation of T cell proliferation / positive regulation of tyrosine phosphorylation of STAT protein / positive regulation of defense response to virus by host / response to cytokine / cytokine activity / transmembrane signaling receptor activity / cytokine-mediated signaling pathway / positive regulation of type II interferon production / scaffold protein binding / negative regulation of neuron apoptotic process / receptor complex / cell surface receptor signaling pathway / defense response to Gram-positive bacterium / inflammatory response / membrane raft / immune response / endoplasmic reticulum lumen / external side of plasma membrane / innate immune response / signaling receptor binding / neuronal cell body / positive regulation of cell population proliferation / dendrite / negative regulation of apoptotic process / cell surface / extracellular space / extracellular exosome / extracellular region / identical protein binding / membrane / plasma membrane / cytosol Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.47 Å | |||||||||
Authors | Caveney NA / Glassman CR / Jude KM / Tsutsumi N / Garcia KC | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Elife / Year: 2022 Title: Structure of the IL-27 quaternary receptor signaling complex. Authors: Nathanael A Caveney / Caleb R Glassman / Kevin M Jude / Naotaka Tsutsumi / K Christopher Garcia / Abstract: Interleukin 27 (IL-27) is a heterodimeric cytokine that functions to constrain T cell-mediated inflammation and plays an important role in immune homeostasis. Binding of IL-27 to cell surface ...Interleukin 27 (IL-27) is a heterodimeric cytokine that functions to constrain T cell-mediated inflammation and plays an important role in immune homeostasis. Binding of IL-27 to cell surface receptors, IL-27Rα and gp130, results in activation of receptor-associated Janus Kinases and nuclear translocation of Signal Transducer and Activator of Transcription 1 (STAT1) and STAT3 transcription factors. Despite the emerging therapeutic importance of this cytokine axis in cancer and autoimmunity, a molecular blueprint of the IL-27 receptor signaling complex, and its relation to other gp130/IL-12 family cytokines, is currently unclear. We used cryogenic-electron microscopy to determine the quaternary structure of IL-27, composed of p28 and Epstein-Barr Virus-Induced 3 (Ebi3) subunits, bound to receptors, IL-27Rα and gp130. The resulting 3.47 Å resolution structure revealed a three-site assembly mechanism nucleated by the central p28 subunit of the cytokine. The overall topology and molecular details of this binding are reminiscent of IL-6 but distinct from related heterodimeric cytokines IL-12 and IL-23. These results indicate distinct receptor assembly mechanisms used by heterodimeric cytokines with important consequences for targeted agonism and antagonism of IL-27 signaling. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_26382.map.gz | 54 MB | EMDB map data format | |
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Header (meta data) | emd-26382-v30.xml emd-26382.xml | 19.9 KB 19.9 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_26382_fsc.xml | 8.5 KB | Display | FSC data file |
Images | emd_26382.png | 55 KB | ||
Masks | emd_26382_msk_1.map | 64 MB | Mask map | |
Others | emd_26382_half_map_1.map.gz emd_26382_half_map_2.map.gz | 59.1 MB 59.1 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-26382 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-26382 | HTTPS FTP |
-Validation report
Summary document | emd_26382_validation.pdf.gz | 695.3 KB | Display | EMDB validaton report |
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Full document | emd_26382_full_validation.pdf.gz | 694.8 KB | Display | |
Data in XML | emd_26382_validation.xml.gz | 15.9 KB | Display | |
Data in CIF | emd_26382_validation.cif.gz | 20.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26382 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26382 | HTTPS FTP |
-Related structure data
Related structure data | 7u7nMC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_26382.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | Sharpened Map | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.839 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_26382_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: IL-27 quaternary receptor signaling complex
File | emd_26382_half_map_1.map | ||||||||||||
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Annotation | IL-27 quaternary receptor signaling complex | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: IL-27 quaternary receptor signaling complex
File | emd_26382_half_map_2.map | ||||||||||||
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Annotation | IL-27 quaternary receptor signaling complex | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : IL-27 quaternary receptor signaling complex
Entire | Name: IL-27 quaternary receptor signaling complex |
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Components |
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-Supramolecule #1: IL-27 quaternary receptor signaling complex
Supramolecule | Name: IL-27 quaternary receptor signaling complex / type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Homo sapiens (human) |
-Macromolecule #1: Interleukin-27 receptor subunit alpha
Macromolecule | Name: Interleukin-27 receptor subunit alpha / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 22.053055 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: AGPLQCYGVG PLGDLNCSWE PLGDLGAPSE LHLQSQKYRS NKTQTVAVAA GRSWVAIPRE QLTMSDKLLV WGTKAGQPLW PPVFVNLET QMKPNAPRLG PDVDFSEDDP LEATVHWAPP TWPSHKVLIC QFHYRRCQEA AWTLLEPELK TIPLTPVEIQ D LELATGYK ...String: AGPLQCYGVG PLGDLNCSWE PLGDLGAPSE LHLQSQKYRS NKTQTVAVAA GRSWVAIPRE QLTMSDKLLV WGTKAGQPLW PPVFVNLET QMKPNAPRLG PDVDFSEDDP LEATVHWAPP TWPSHKVLIC QFHYRRCQEA AWTLLEPELK TIPLTPVEIQ D LELATGYK VYGRCRMEKE EDLWGEWSPI LSFQTPPS |
-Macromolecule #2: Interleukin-6 receptor subunit beta
Macromolecule | Name: Interleukin-6 receptor subunit beta / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 34.099535 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: ELLDPCGYIS PESPVVQLHS NFTAVCVLKE KCMDYFHVNA NYIVWKTNHF TIPKEQYTII NRTASSVTFT DIASLNIQLT CNILTFGQL EQNVYGITII SGLPPEKPKN LSCIVNEGKK MRCEWDGGRE THLETNFTLK SEWATHKFAD CKAKRDTPTS C TVDYSTVY ...String: ELLDPCGYIS PESPVVQLHS NFTAVCVLKE KCMDYFHVNA NYIVWKTNHF TIPKEQYTII NRTASSVTFT DIASLNIQLT CNILTFGQL EQNVYGITII SGLPPEKPKN LSCIVNEGKK MRCEWDGGRE THLETNFTLK SEWATHKFAD CKAKRDTPTS C TVDYSTVY FVNIEVWVEA ENALGKVTSD HINFDPVYKV KPNPPHNLSV INSEELSSIL KLTWTNPSIK SVIILKYNIQ YR TKDASTW SQIPPEDTAS TRSSFTVQDL KPFTEYVFRI RCMKEDGKGY WSDWSEEASG IT |
-Macromolecule #3: Interleukin-27 subunit beta
Macromolecule | Name: Interleukin-27 subunit beta / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 23.209553 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: RKGPPAALTL PRVQCRASRY PIAVDCSWTL PPAPNSTSPV SFIATYRLGM AARGHSWPCL QQTPTSTSCT ITDVQLFSMA PYVLNVTAV HPWGSSSSFV PFITEHIIKP DPPEGVRLSP LAERQLQVQW EPPGSWPFPE IFSLKYWIRY KRQGAARFHR V GPIEATSF ...String: RKGPPAALTL PRVQCRASRY PIAVDCSWTL PPAPNSTSPV SFIATYRLGM AARGHSWPCL QQTPTSTSCT ITDVQLFSMA PYVLNVTAV HPWGSSSSFV PFITEHIIKP DPPEGVRLSP LAERQLQVQW EPPGSWPFPE IFSLKYWIRY KRQGAARFHR V GPIEATSF ILRAVRPRAR YYVQVAAQDL TDYGELSDWS LPATATMSLG |
-Macromolecule #4: Interleukin-27 subunit alpha
Macromolecule | Name: Interleukin-27 subunit alpha / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 24.56216 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: FPRPPGRPQL SLQELRREFT VSLHLARKLL SEVRGQAHRF AESHLPGVNL YLLPLGEQLP DVSLTFQAWR RLSDPERLCF ISTTLQPFH ALLGGLGTQG RWTNMERMQL WAMRLDLRDL QRHLRFQVLA AGFNLPEEEE EEEEEEEEER KGLLPGALGS A LQGPAQVS ...String: FPRPPGRPQL SLQELRREFT VSLHLARKLL SEVRGQAHRF AESHLPGVNL YLLPLGEQLP DVSLTFQAWR RLSDPERLCF ISTTLQPFH ALLGGLGTQG RWTNMERMQL WAMRLDLRDL QRHLRFQVLA AGFNLPEEEE EEEEEEEEER KGLLPGALGS A LQGPAQVS WPQLLSTYRL LHSLELVLSR AVRELLLLSK AGHSVWPLGF PTLSPQP |
-Macromolecule #8: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 8 / 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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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 1 mg/mL | |||||||||
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Buffer | pH: 8 Component:
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Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 200 / Pretreatment - Type: GLOW DISCHARGE | |||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277.15 K / Instrument: FEI VITROBOT MARK IV Details: The grids were blotted for 3 seconds with an offset of 3.. |
-Electron microscopy
Microscope | TFS KRIOS |
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Specialist optics | Energy filter - Name: GIF Bioquantum |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: OTHER / Imaging mode: OTHER / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.8 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |