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- PDB-8d82: Cryo-EM structure of human IL-6 signaling complex in detergent: m... -
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Open data
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Basic information
Entry | Database: PDB / ID: 8d82 | ||||||
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Title | Cryo-EM structure of human IL-6 signaling complex in detergent: model containing full extracellular domains | ||||||
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![]() | CYTOKINE / cytokine signaling / IL-6 / IL-6R alpha / gp130 | ||||||
Function / homology | ![]() ciliary neurotrophic factor binding / positive regulation of interleukin-21 production / regulation of astrocyte activation / glucagon secretion / interleukin-6 receptor activity / interleukin-6 binding / regulation of glucagon secretion / hepatic immune response / oncostatin-M-mediated signaling pathway / negative regulation of interleukin-1-mediated signaling pathway ...ciliary neurotrophic factor binding / positive regulation of interleukin-21 production / regulation of astrocyte activation / glucagon secretion / interleukin-6 receptor activity / interleukin-6 binding / regulation of glucagon secretion / hepatic immune response / oncostatin-M-mediated signaling pathway / negative regulation of interleukin-1-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 / regulation of vascular endothelial growth factor production / oncostatin-M receptor complex / negative regulation of primary miRNA processing / ciliary neurotrophic factor receptor binding / interleukin-11 receptor activity / interleukin-11 binding / T follicular helper cell differentiation / ciliary neurotrophic factor-mediated signaling pathway / germinal center B cell differentiation / ciliary neurotrophic factor receptor complex / interleukin-27-mediated signaling pathway / interleukin-6 receptor complex / positive regulation of extracellular matrix disassembly / positive regulation of receptor signaling pathway via STAT / positive regulation of apoptotic DNA fragmentation / response to peptidoglycan / positive regulation of type B pancreatic cell apoptotic process / regulation of microglial cell activation / hepatocyte proliferation / neutrophil apoptotic process / interleukin-6 receptor binding / negative regulation of collagen biosynthetic process / : / interleukin-11-mediated signaling pathway / inflammatory response to wounding / T-helper 17 cell lineage commitment / positive regulation of T-helper 2 cell cytokine production / positive regulation of adaptive immune response / positive regulation of B cell activation / endocrine pancreas development / positive regulation of glomerular mesangial cell proliferation / negative regulation of interleukin-8 production / positive regulation of acute inflammatory response / regulation of neuroinflammatory response / vascular endothelial growth factor production / positive regulation of astrocyte differentiation / negative regulation of chemokine production / positive regulation of neuroinflammatory response / positive regulation of leukocyte chemotaxis / intestinal epithelial cell development / positive regulation of platelet aggregation / positive regulation of cytokine production involved in inflammatory response / neutrophil mediated immunity / Interleukin-27 signaling / IL-6-type cytokine receptor ligand interactions / Interleukin-35 Signalling / cytokine receptor activity / negative regulation of bone resorption / positive regulation of leukocyte adhesion to vascular endothelial cell / CD163 mediating an anti-inflammatory response / positive regulation of immunoglobulin production / glycogen metabolic process / interleukin-6-mediated signaling pathway / maintenance of blood-brain barrier / Interleukin-6 signaling / positive regulation of Notch signaling pathway / negative regulation of fat cell differentiation / protein tyrosine kinase activator activity / positive regulation of cardiac muscle hypertrophy / MAPK3 (ERK1) activation / monocyte chemotaxis / growth factor binding / positive regulation of interleukin-17 production / Interleukin-10 signaling / cytokine binding / MAPK1 (ERK2) activation / regulation of insulin secretion / positive regulation of interleukin-10 production / humoral immune response / negative regulation of lipid storage / Transcriptional Regulation by VENTX / positive regulation of vascular endothelial growth factor production / regulation of angiogenesis / positive regulation of osteoblast differentiation / coreceptor activity / positive regulation of epithelial to mesenchymal transition / positive regulation of chemokine production / extrinsic apoptotic signaling pathway / positive regulation of T cell proliferation / response to glucocorticoid / positive regulation of tyrosine phosphorylation of STAT protein / positive regulation of glial cell proliferation / positive regulation of interleukin-1 beta production / response to activity / response to cytokine / cytokine activity Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.22 Å | ||||||
![]() | Zhou, Y. / Franklin, M.C. | ||||||
Funding support | 1items
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![]() | ![]() 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: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 391.5 KB | Display | ![]() |
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PDB format | ![]() | 319.7 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 27244MC ![]() 8d6aC ![]() 8d74C ![]() 8d7eC ![]() 8d7hC ![]() 8d7rC ![]() 8d85C M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 38694.320 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #2: Protein | Mass: 20837.770 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #3: Protein | Mass: 77085.125 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #4: 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 #5: Sugar | ChemComp-NAG / 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 |
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Sample preparation
Component | Name: Human IL-6 in complex with IL-6R alpha and detergent-solubilized gp130 Type: COMPLEX / Entity ID: #1-#3 / Source: RECOMBINANT |
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Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() ![]() |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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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: ![]() |
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) |
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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: C2 (2 fold cyclic) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.22 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 105760 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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