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Yorodumi- PDB-8d74: Cryo-EM structure of human CNTF signaling complex: model containi... -
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-Basic information
Entry | Database: PDB / ID: 8d74 | ||||||
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Title | Cryo-EM structure of human CNTF signaling complex: model containing the interaction core region | ||||||
Components |
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Keywords | CYTOKINE / cytokine signaling / CNTF / CNTFR alpha / gp130 / LIFR | ||||||
Function / homology | Function and homology information CNTFR-CLCF1 complex / skeletal muscle organ development / leukemia inhibitory factor receptor activity / oncostatin-M receptor activity / retinal rod cell differentiation / oncostatin-M-mediated signaling pathway / regulation of retinal cell programmed cell death / ciliary neurotrophic factor receptor activity / muscle organ morphogenesis / negative regulation of interleukin-6-mediated signaling pathway ...CNTFR-CLCF1 complex / skeletal muscle organ development / leukemia inhibitory factor receptor activity / oncostatin-M receptor activity / retinal rod cell differentiation / oncostatin-M-mediated signaling pathway / regulation of retinal cell programmed cell death / ciliary neurotrophic factor receptor activity / muscle organ morphogenesis / 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 / RUNX1 regulates transcription of genes involved in interleukin signaling / interleukin-6 receptor activity / interleukin-6 binding / ciliary neurotrophic factor-mediated signaling pathway / negative regulation of photoreceptor cell differentiation / ciliary neurotrophic factor receptor complex / interleukin-27-mediated signaling pathway / interleukin-6 receptor complex / interleukin-6 receptor binding / brainstem development / interleukin-11-mediated signaling pathway / T-helper 17 cell lineage commitment / sex differentiation / positive regulation of adaptive immune response / positive regulation of acute inflammatory response / positive regulation of astrocyte differentiation / intestinal epithelial cell development / negative regulation of motor neuron apoptotic process / positive regulation of platelet aggregation / Interleukin-27 signaling / IL-6-type cytokine receptor ligand interactions / Interleukin-35 Signalling / motor neuron apoptotic process / cytokine receptor activity / extrinsic component of membrane / glycogen metabolic process / interleukin-6-mediated signaling pathway / Interleukin-6 signaling / positive regulation of Notch signaling pathway / suckling behavior / protein tyrosine kinase activator activity / positive regulation of cardiac muscle hypertrophy / cytokine binding / positive regulation of axon regeneration / MAPK3 (ERK1) activation / growth factor binding / MAPK1 (ERK2) activation / positive regulation of vascular endothelial growth factor production / neuron development / positive regulation of osteoblast differentiation / coreceptor activity / positive regulation of T cell proliferation / positive regulation of tyrosine phosphorylation of STAT protein / response to cytokine / cytokine activity / astrocyte activation / growth factor activity / cytokine-mediated signaling pathway / nervous system development / scaffold protein binding / negative regulation of neuron apoptotic process / cell surface receptor signaling pathway / receptor complex / membrane raft / apical plasma membrane / external side of plasma membrane / axon / signaling receptor binding / neuronal cell body / dendrite / positive regulation of cell population proliferation / positive regulation of gene expression / protein-containing complex binding / negative regulation of apoptotic process / signal transduction / extracellular space / extracellular exosome / extracellular region / identical protein binding / membrane / plasma membrane / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.03 Å | ||||||
Authors | Zhou, Y. / Franklin, M.C. | ||||||
Funding support | 1items
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Citation | Journal: 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 |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8d74.cif.gz | 240 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8d74.ent.gz | 183.9 KB | Display | PDB format |
PDBx/mmJSON format | 8d74.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8d74_validation.pdf.gz | 1.6 MB | Display | wwPDB validaton report |
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Full document | 8d74_full_validation.pdf.gz | 1.6 MB | Display | |
Data in XML | 8d74_validation.xml.gz | 46.8 KB | Display | |
Data in CIF | 8d74_validation.cif.gz | 66.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/d7/8d74 ftp://data.pdbj.org/pub/pdb/validation_reports/d7/8d74 | HTTPS FTP |
-Related structure data
Related structure data | 27227MC 8d6aC 8d7eC 8d7hC 8d7rC 8d82C 8d85C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Protein , 2 types, 2 molecules AB
#1: Protein | 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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#4: Protein | Mass: 92834.812 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: LIFR / Production host: Cricetulus griseus (Chinese hamster) / References: UniProt: P42702 |
-Ciliary neurotrophic ... , 2 types, 2 molecules DC
#2: Protein | Mass: 24704.854 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CNTF / Production host: Cricetulus griseus (Chinese hamster) / References: UniProt: P26441 |
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#3: Protein | Mass: 35855.305 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CNTFR / Production host: Cricetulus griseus (Chinese hamster) / References: UniProt: P26992 |
-Sugars , 2 types, 12 molecules
#5: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #6: Sugar | ChemComp-NAG / |
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-Details
Has ligand of interest | N |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Human CNTF in complex with CNTFR alpha, gp130, and LIFR Type: COMPLEX / Entity ID: #1-#4 / Source: RECOMBINANT |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Cricetulus griseus (Chinese hamster) |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2600 nm / Nominal defocus min: 1400 nm |
Image recording | Electron dose: 40 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.17.1_3660: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.03 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 250735 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
Displacement parameters | Biso mean: 82.41 Å2 | ||||||||||||||||||||||||
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