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- PDB-8d85: Cryo-EM structure of human IL-27 signaling complex: model contain... -

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Basic information

Entry
Database: PDB / ID: 8d85
TitleCryo-EM structure of human IL-27 signaling complex: model containing the interaction core region
Components
  • (Interleukin-27 subunit ...) x 2
  • Interleukin-27 receptor subunit alpha
  • Interleukin-6 receptor subunit beta
KeywordsCYTOKINE / cytokine signaling / IL-27 / IL-27R alpha / gp130 / EBI3 / p28
Function / homology
Function and homology information


negative regulation of T cell extravasation / interleukin-27 receptor binding / regulation of T-helper 1 cell differentiation / negative regulation of T-helper 17 type immune response / interleukin-27 receptor activity / ciliary neurotrophic factor receptor activity / oncostatin-M-mediated signaling pathway / leukemia inhibitory factor signaling pathway / regulation of isotype switching to IgG isotypes / negative regulation of interleukin-6-mediated signaling pathway ...negative regulation of T cell extravasation / interleukin-27 receptor binding / regulation of T-helper 1 cell differentiation / negative regulation of T-helper 17 type immune response / interleukin-27 receptor activity / ciliary neurotrophic factor receptor activity / oncostatin-M-mediated signaling pathway / leukemia inhibitory factor signaling pathway / regulation of isotype switching to IgG isotypes / negative regulation of interleukin-6-mediated signaling pathway / negative regulation of type 2 immune response / oncostatin-M receptor complex / ciliary neurotrophic factor receptor binding / ciliary neurotrophic factor-mediated signaling pathway / interleukin-11 receptor activity / interleukin-11 binding / ciliary neurotrophic factor receptor complex / interleukin-6 receptor complex / response to Gram-positive bacterium / interleukin-27-mediated signaling pathway / 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 / positive regulation of astrocyte differentiation / intestinal epithelial cell development / IL-6-type cytokine receptor ligand interactions / Interleukin-27 signaling / Interleukin-35 Signalling / negative regulation of interleukin-17 production / positive regulation of platelet aggregation / cell surface receptor signaling pathway via STAT / cytokine receptor activity / Interleukin-6 signaling / T-helper 1 type immune response / MAPK3 (ERK1) activation / glycogen metabolic process / interleukin-6-mediated signaling pathway / positive regulation of Notch signaling pathway / growth factor binding / MAPK1 (ERK2) activation / positive regulation of cardiac muscle hypertrophy / cytokine binding / negative regulation of interleukin-6 production / regulation of T cell proliferation / protein tyrosine kinase activator activity / humoral immune response / negative regulation of tumor necrosis factor production / positive regulation of vascular endothelial growth factor production / positive regulation of osteoblast differentiation / positive regulation of T cell proliferation / T cell proliferation / coreceptor activity / positive regulation of defense response to virus by host / response to cytokine / cytokine activity / cytokine-mediated signaling pathway / positive regulation of type II interferon production / transmembrane signaling receptor activity / scaffold protein binding / negative regulation of neuron apoptotic process / receptor complex / cell surface receptor signaling pathway / defense response to Gram-positive bacterium / immune response / inflammatory response / membrane raft / endoplasmic reticulum lumen / external side of plasma membrane / signaling receptor binding / innate immune response / 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
Interleukin-27 alpha / IL27B N-terminal FN3 domain / : / : / : / Type I cytokine receptor, cytokine-binding domain / Long hematopoietin receptor, soluble alpha chain, conserved site / Long hematopoietin receptor, soluble alpha chains family signature. / Interleukin-6 receptor alpha chain, binding / Immunoglobulin C2-set-like, ligand-binding ...Interleukin-27 alpha / IL27B N-terminal FN3 domain / : / : / : / Type I cytokine receptor, cytokine-binding domain / Long hematopoietin receptor, soluble alpha chain, conserved site / Long hematopoietin receptor, soluble alpha chains family signature. / Interleukin-6 receptor alpha chain, binding / Immunoglobulin C2-set-like, ligand-binding / Ig-like C2-type domain / Long hematopoietin receptor, Gp130 family 2, conserved site / Long hematopoietin receptor, gp130 family signature. / Growth Hormone; Chain: A; - #10 / Four-helical cytokine-like, core / Growth Hormone; Chain: A; / Fibronectin type III domain / Fibronectin type 3 domain / Fibronectin type-III domain profile. / Fibronectin type III / Fibronectin type III superfamily / Immunoglobulin-like fold / Immunoglobulins / Up-down Bundle / Immunoglobulin-like / Sandwich / Mainly Beta / Mainly Alpha
Similarity search - Domain/homology
Interleukin-6 receptor subunit beta / Interleukin-27 subunit beta / Interleukin-27 receptor subunit alpha / Interleukin-27 subunit alpha
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.81 Å
AuthorsZhou, Y. / Franklin, M.C.
Funding support1items
OrganizationGrant numberCountry
Other private
CitationJournal: Sci Adv / Year: 2023
Title: Structural insights into the assembly of gp130 family cytokine signaling complexes.
Authors: Yi Zhou / Panayiotis E Stevis / Jing Cao / Kei Saotome / Jiaxi Wu / Arielle Glatman Zaretsky / Sokol Haxhinasto / George D Yancopoulos / Andrew J Murphy / Mark W Sleeman / William C Olson / Matthew C Franklin /
Abstract: The interleukin-6 (IL-6) family cytokines signal through gp130 receptor homodimerization or heterodimerization with a second signaling receptor and play crucial roles in various cellular processes. ...The interleukin-6 (IL-6) family cytokines signal through gp130 receptor homodimerization or heterodimerization with a second signaling receptor and play crucial roles in various cellular processes. We determined cryo-electron microscopy structures of five signaling complexes of this family, containing full receptor ectodomains bound to their respective ligands ciliary neurotrophic factor, cardiotrophin-like cytokine factor 1 (CLCF1), leukemia inhibitory factor, IL-27, and IL-6. Our structures collectively reveal similarities and differences in the assembly of these complexes. The acute bends at both signaling receptors in all complexes bring the membrane-proximal domains to a ~30 angstrom range but with distinct distances and orientations. We also reveal how CLCF1 engages its secretion chaperone cytokine receptor-like factor 1. Our data provide valuable insights for therapeutically targeting gp130-mediated signaling.
History
DepositionJun 7, 2022Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 29, 2023Provider: repository / Type: Initial release
Revision 1.0Mar 29, 2023Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0Mar 29, 2023Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
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Revision 1.0Mar 29, 2023Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Mar 29, 2023Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release
Revision 1.0Mar 29, 2023Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Mar 29, 2023Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Mar 29, 2023Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Mar 29, 2023Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release
Revision 1.1Oct 23, 2024Group: Data collection / Structure summary
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / em_admin / pdbx_entry_details / pdbx_modification_feature
Item: _em_admin.last_update / _pdbx_entry_details.has_protein_modification
Revision 1.2May 28, 2025Group: Data collection / Category: em_admin / em_software / Item: _em_admin.last_update / _em_software.name
Revision 1.1May 28, 2025Data content type: EM metadata / Data content type: EM metadata / EM metadata / Group: Data processing / Experimental summary / Data content type: EM metadata / EM metadata / Category: em_admin / em_software / Data content type: EM metadata / EM metadata / Item: _em_admin.last_update / _em_software.name

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
C: Interleukin-27 subunit beta
D: Interleukin-27 subunit alpha
A: Interleukin-27 receptor subunit alpha
B: Interleukin-6 receptor subunit beta
hetero molecules


Theoretical massNumber of molelcules
Total (without water)180,77312
Polymers178,3944
Non-polymers2,3798
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

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Interleukin-27 subunit ... , 2 types, 2 molecules CD

#1: Protein Interleukin-27 subunit beta / IL-27 subunit beta / IL-27B / Epstein-Barr virus-induced gene 3 protein / EBV-induced gene 3 protein


Mass: 23338.732 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: EBI3, IL27B / Production host: Cricetulus griseus (Chinese hamster) / References: UniProt: Q14213
#2: Protein Interleukin-27 subunit alpha / IL-27 subunit alpha / IL-27-A / IL27-A / Interleukin-30 / p28


Mass: 27877.730 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: IL27, IL27A, IL30 / Production host: Cricetulus griseus (Chinese hamster) / References: UniProt: Q8NEV9

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Protein , 2 types, 2 molecules AB

#3: Protein Interleukin-27 receptor subunit alpha / IL-27 receptor subunit alpha / IL-27R subunit alpha / IL-27R-alpha / IL-27RA / Cytokine receptor ...IL-27 receptor subunit alpha / IL-27R subunit alpha / IL-27R-alpha / IL-27RA / Cytokine receptor WSX-1 / Cytokine receptor-like 1 / Type I T-cell cytokine receptor / TCCR / ZcytoR1


Mass: 55944.184 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: IL27RA, CRL1, TCCR, WSX1, UNQ296/PRO336 / Production host: Cricetulus griseus (Chinese hamster) / References: UniProt: Q6UWB1
#4: Protein Interleukin-6 receptor subunit beta / IL-6 receptor subunit beta / IL-6R subunit beta / IL-6R-beta / IL-6RB / CDw130 / Interleukin-6 ...IL-6 receptor subunit beta / IL-6R subunit beta / IL-6R-beta / IL-6RB / CDw130 / Interleukin-6 signal transducer / Membrane glycoprotein 130 / gp130 / Oncostatin-M receptor subunit alpha


Mass: 71233.203 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: IL6ST / Production host: Cricetulus griseus (Chinese hamster) / References: UniProt: P40189

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Sugars , 2 types, 8 molecules

#5: Polysaccharide 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 424.401 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DGlcpNAcb1-4DGlcpNAcb1-ROHGlycam Condensed SequenceGMML 1.0
WURCS=2.0/1,2,1/[a2122h-1b_1-5_2*NCC/3=O]/1-1/a4-b1WURCSPDB2Glycan 1.1.0
[][D-1-deoxy-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{}}LINUCSPDB-CARE
#6: Sugar
ChemComp-NAG / 2-acetamido-2-deoxy-beta-D-glucopyranose / N-acetyl-beta-D-glucosamine / 2-acetamido-2-deoxy-beta-D-glucose / 2-acetamido-2-deoxy-D-glucose / 2-acetamido-2-deoxy-glucose / N-ACETYL-D-GLUCOSAMINE


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 5 / Source method: obtained synthetically / Formula: C8H15NO6
IdentifierTypeProgram
DGlcpNAcbCONDENSED IUPAC CARBOHYDRATE SYMBOLGMML 1.0
N-acetyl-b-D-glucopyranosamineCOMMON NAMEGMML 1.0
b-D-GlcpNAcIUPAC CARBOHYDRATE SYMBOLPDB-CARE 1.0
GlcNAcSNFG CARBOHYDRATE SYMBOLGMML 1.0

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Details

Has ligand of interestN
Has protein modificationY

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Experimental details

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Experiment

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

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Sample preparation

ComponentName: Human IL-27 in complex with IL-27R alpha and gp130 / Type: COMPLEX / Entity ID: #1-#4 / Source: RECOMBINANT
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Cricetulus griseus (Chinese hamster)
Buffer solutionpH: 7.5
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

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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 FIELD / Nominal defocus max: 2600 nm / Nominal defocus min: 1400 nm
Image recordingElectron dose: 40 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k)

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Processing

SoftwareName: PHENIX / Version: 1.17.1_3660: / Classification: refinement
EM softwareName: PHENIX / Category: model refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
SymmetryPoint symmetry: C1 (asymmetric)
3D reconstructionResolution: 3.81 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 139752 / Symmetry type: POINT
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.0027297
ELECTRON MICROSCOPYf_angle_d0.4639952
ELECTRON MICROSCOPYf_dihedral_angle_d19.8991004
ELECTRON MICROSCOPYf_chiral_restr0.0391129
ELECTRON MICROSCOPYf_plane_restr0.0031258

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