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Yorodumi- PDB-5fuc: Biophysical and cellular characterisation of a junctional epitope... -
+Open data
-Basic information
Entry | Database: PDB / ID: 5fuc | ||||||
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Title | Biophysical and cellular characterisation of a junctional epitope antibody that locks IL-6 and gp80 together in a stable complex: implications for new therapeutic strategies | ||||||
Components |
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Keywords | IMMUNE SYSTEM / VHH / IL-6 / IL-6 RECEPTOR ALPHA / IL-6 RECEPTOR BETA / GP80 / ANTIBODY / JUNCTIONAL EPITOPE | ||||||
Function / homology | Function and homology information 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 / negative regulation of interleukin-1-mediated signaling pathway / regulation of vascular endothelial growth factor production ...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 / negative regulation of interleukin-1-mediated signaling pathway / regulation of vascular endothelial growth factor production / negative regulation of primary miRNA processing / 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-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 / : / inflammatory response to wounding / T-helper 17 cell lineage commitment / positive regulation of T-helper 2 cell cytokine production / 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 / negative regulation of chemokine production / positive regulation of neuroinflammatory response / positive regulation of leukocyte chemotaxis / positive regulation of platelet aggregation / positive regulation of cytokine production involved in inflammatory response / neutrophil mediated immunity / negative regulation of lipid storage / 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 / interleukin-6-mediated signaling pathway / maintenance of blood-brain barrier / Interleukin-6 signaling / negative regulation of fat cell differentiation / MAPK3 (ERK1) activation / monocyte chemotaxis / positive regulation of interleukin-17 production / Interleukin-10 signaling / MAPK1 (ERK2) activation / regulation of insulin secretion / positive regulation of glial cell proliferation / positive regulation of interleukin-10 production / humoral immune response / Transcriptional Regulation by VENTX / positive regulation of vascular endothelial growth factor production / regulation of angiogenesis / positive regulation of osteoblast differentiation / 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 / liver regeneration / positive regulation of smooth muscle cell proliferation / positive regulation of interleukin-1 beta production / response to activity / response to cytokine / cytokine activity / acute-phase response / positive regulation of interleukin-8 production / positive regulation of translation / Transcriptional regulation of granulopoiesis / Post-translational protein phosphorylation / positive regulation of receptor signaling pathway via JAK-STAT / positive regulation of DNA-binding transcription factor activity / growth factor activity / platelet activation / cellular response to virus / negative regulation of neurogenesis / cytokine-mediated signaling pathway / cellular response to hydrogen peroxide / neuron cellular homeostasis / ADORA2B mediated anti-inflammatory cytokines production / positive regulation of interleukin-6 production / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / positive regulation of peptidyl-tyrosine phosphorylation / positive regulation of peptidyl-serine phosphorylation / positive regulation of tumor necrosis factor production Similarity search - Function | ||||||
Biological species | HOMO SAPIENS (human) CAMELUS DROMEDARIUS (Arabian camel) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.7 Å | ||||||
Authors | Adams, R. / Griffin, R. / Doyle, C. / Ettorre, A. | ||||||
Citation | Journal: Sci Rep / Year: 2017 Title: Discovery of a junctional epitope antibody that stabilizes IL-6 and gp80 protein:protein interaction and modulates its downstream signaling. Authors: Adams, R. / Burnley, R.J. / Valenzano, C.R. / Qureshi, O. / Doyle, C. / Lumb, S. / Del Carmen Lopez, M. / Griffin, R. / McMillan, D. / Taylor, R.D. / Meier, C. / Mori, P. / Griffin, L.M. / ...Authors: Adams, R. / Burnley, R.J. / Valenzano, C.R. / Qureshi, O. / Doyle, C. / Lumb, S. / Del Carmen Lopez, M. / Griffin, R. / McMillan, D. / Taylor, R.D. / Meier, C. / Mori, P. / Griffin, L.M. / Wernery, U. / Kinne, J. / Rapecki, S. / Baker, T.S. / Lawson, A.D. / Wright, M. / Ettorre, A. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5fuc.cif.gz | 200.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5fuc.ent.gz | 159.8 KB | Display | PDB format |
PDBx/mmJSON format | 5fuc.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 5fuc_validation.pdf.gz | 492.1 KB | Display | wwPDB validaton report |
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Full document | 5fuc_full_validation.pdf.gz | 514.2 KB | Display | |
Data in XML | 5fuc_validation.xml.gz | 37.2 KB | Display | |
Data in CIF | 5fuc_validation.cif.gz | 50.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/fu/5fuc ftp://data.pdbj.org/pub/pdb/validation_reports/fu/5fuc | HTTPS FTP |
-Related structure data
Related structure data | 1p9mS S: Starting model for refinement |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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2 |
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Unit cell |
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-Components
#1: Protein | Mass: 18982.682 Da / Num. of mol.: 2 / Fragment: RESIDUES 49-212 Source method: isolated from a genetically manipulated source Source: (gene. exp.) HOMO SAPIENS (human) / Production host: ESCHERICHIA COLI (E. coli) / References: UniProt: P05231 #2: Protein | Mass: 25973.068 Da / Num. of mol.: 2 / Fragment: RESIDUES 20-33 AND RESIDUES 111-322 / Mutation: YES Source method: isolated from a genetically manipulated source Source: (gene. exp.) HOMO SAPIENS (human) / Cell line (production host): HEK293 / Production host: HOMO SAPIENS (human) / References: UniProt: D6R9R8, UniProt: P08887 #3: Antibody | Mass: 14677.187 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) CAMELUS DROMEDARIUS (Arabian camel) / Cell line (production host): HEK293 / Production host: HOMO SAPIENS (human) #4: Sugar | ChemComp-NAG / #5: Water | ChemComp-HOH / | Sequence details | CYS 192 MUTATED TO SER, CYS 258 MUTATED TO ALA. THE FIRST 19 RESIDUES ARE FROM DOMAIN 1 OF IL-6. ...CYS 192 MUTATED TO SER, CYS 258 MUTATED TO ALA. THE FIRST 19 RESIDUES ARE FROM DOMAIN 1 OF IL-6. THE REST OF THE SEQUENCE IS DOMAIN 3. RENLYFQ IS REMAINDER OF TEV CLEAVAGE SITE VHH6 IS INTERNAL DISCOVERY | |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.4 Å3/Da / Density % sol: 49 % / Description: NONE |
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Crystal grow | Details: 0.1 M MES, PH 6.5, 14% PEG20K |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: SOLEIL / Beamline: PROXIMA 1 / Wavelength: 0.97857 |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Sep 12, 2014 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97857 Å / Relative weight: 1 |
Reflection | Resolution: 2.69→50 Å / Num. obs: 18151 / % possible obs: 99.4 % / Observed criterion σ(I): 3 / Redundancy: 7.5 % / Rmerge(I) obs: 0.07 / Net I/σ(I): 20.88 |
Reflection shell | Resolution: 2.69→2.86 Å / Redundancy: 7.5 % / Rmerge(I) obs: 0.5 / Mean I/σ(I) obs: 3.97 / % possible all: 96.9 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB ENTRY 1P9M, VHH IN-HOUSE STRUCTURE Resolution: 2.7→20 Å / Rfactor Rfree error: 0.005 / Data cutoff high absF: 10000 / Data cutoff low absF: 0 / Cross valid method: THROUGHOUT / σ(F): 0 Details: THE FOLLOWING REGIONS WERE TOO DISORDERED TO MODEL, CHAIN A RESIDUES 52 TO 62, 131 TO 133, CHAIN B RESIDUES 19 AND 20, 132 TO 135, CHAIN C RESIDUES 73 TO 97, 138, 298 TO 303, CHAIN D ...Details: THE FOLLOWING REGIONS WERE TOO DISORDERED TO MODEL, CHAIN A RESIDUES 52 TO 62, 131 TO 133, CHAIN B RESIDUES 19 AND 20, 132 TO 135, CHAIN C RESIDUES 73 TO 97, 138, 298 TO 303, CHAIN D RESIDUES 73 TO 91, 134 TO 140, 299 TO 303, CHAIN E RESIDUES 1 AND 2, 8 TO 16, 121 TO 132, CHAIN V RESIDUES 125 TO 132
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Displacement parameters |
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Refinement step | Cycle: LAST / Resolution: 2.7→20 Å
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LS refinement shell | Resolution: 2.7→2.8 Å / Rfactor Rfree error: 0.026 / Total num. of bins used: 10
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