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- EMDB-36003: Cryo-EM structure of the Tocilizumab Fab/IL-6R complex -

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Basic information

Entry
Database: EMDB / ID: EMD-36003
TitleCryo-EM structure of the Tocilizumab Fab/IL-6R complex
Map data
Sample
  • Complex: the tocilizumab Fab/IL-6R complex
    • Protein or peptide: Heavy chain of Tocilizumab Fab
    • Protein or peptide: Light chain of Tocilizumab Fab
    • Protein or peptide: Interleukin-6 receptor subunit alpha
    • Protein or peptide: IL6R-D2 peptide
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
Keywordsantibody / IL-6R / structural protein / IMMUNE SYSTEM
Function / homology
Function and homology information


ciliary neurotrophic factor binding / interleukin-6 receptor activity / interleukin-6 binding / hepatic immune response / interleukin-11 receptor activity / interleukin-11 binding / ciliary neurotrophic factor receptor complex / ciliary neurotrophic factor-mediated signaling pathway / interleukin-6 receptor complex / negative regulation of collagen biosynthetic process ...ciliary neurotrophic factor binding / interleukin-6 receptor activity / interleukin-6 binding / hepatic immune response / interleukin-11 receptor activity / interleukin-11 binding / ciliary neurotrophic factor receptor complex / ciliary neurotrophic factor-mediated signaling pathway / interleukin-6 receptor complex / negative regulation of collagen biosynthetic process / positive regulation of activation of Janus kinase activity / T-helper 17 cell lineage commitment / positive regulation of glomerular mesangial cell proliferation / endocrine pancreas development / negative regulation of interleukin-8 production / vascular endothelial growth factor production / positive regulation of leukocyte chemotaxis / neutrophil mediated immunity / cytokine receptor activity / Interleukin-6 signaling / interleukin-6-mediated signaling pathway / MAPK3 (ERK1) activation / MAPK1 (ERK2) activation / monocyte chemotaxis / positive regulation of osteoblast differentiation / positive regulation of chemokine production / extrinsic apoptotic signaling pathway / positive regulation of tyrosine phosphorylation of STAT protein / response to cytokine / acute-phase response / positive regulation of smooth muscle cell proliferation / cytokine-mediated signaling pathway / positive regulation of interleukin-6 production / Transcriptional regulation of granulopoiesis / positive regulation of peptidyl-tyrosine phosphorylation / Interleukin-4 and Interleukin-13 signaling / defense response to Gram-negative bacterium / Potential therapeutics for SARS / positive regulation of MAPK cascade / receptor complex / defense response to Gram-positive bacterium / apical plasma membrane / external side of plasma membrane / positive regulation of cell population proliferation / enzyme binding / protein homodimerization activity / extracellular space / extracellular region / plasma membrane
Similarity search - Function
Type I cytokine receptor, cytokine-binding domain / Interleukin-6 receptor alpha chain, binding / Long hematopoietin receptor, soluble alpha chain, conserved site / Long hematopoietin receptor, soluble alpha chains family signature. / Immunoglobulin / Immunoglobulin domain / Fibronectin type 3 domain / Immunoglobulin subtype 2 / Immunoglobulin C-2 Type / Fibronectin type-III domain profile. ...Type I cytokine receptor, cytokine-binding domain / Interleukin-6 receptor alpha chain, binding / Long hematopoietin receptor, soluble alpha chain, conserved site / Long hematopoietin receptor, soluble alpha chains family signature. / Immunoglobulin / Immunoglobulin domain / Fibronectin type 3 domain / Immunoglobulin subtype 2 / Immunoglobulin C-2 Type / Fibronectin type-III domain profile. / Fibronectin type III / Fibronectin type III superfamily / Immunoglobulin subtype / Immunoglobulin / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / Immunoglobulin-like fold
Similarity search - Domain/homology
Interleukin-6 receptor subunit alpha
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.3 Å
AuthorsShe J / Chen L
Funding support China, 1 items
OrganizationGrant numberCountry
Ministry of Science and Technology (MoST, China)2021YFF0600800 China
CitationJournal: To Be Published
Title: Cryo-EM structures of tocilizumab and sarilumab Fabs in complex with IL-6R
Authors: She J / Wang MX
History
DepositionApr 25, 2023-
Header (metadata) releaseMar 27, 2024-
Map releaseMar 27, 2024-
UpdateMar 27, 2024-
Current statusMar 27, 2024Processing site: PDBj / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_36003.map.gz / Format: CCP4 / Size: 216 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Voxel sizeX=Y=Z: 0.82 Å
Density
Contour LevelBy AUTHOR: 0.1
Minimum - Maximum-1.5053748 - 2.2731018
Average (Standard dev.)-0.00023687196 (±0.019807989)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions384384384
Spacing384384384
CellA=B=C: 314.88 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_36003_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: #1

Fileemd_36003_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Sample components

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Entire : the tocilizumab Fab/IL-6R complex

EntireName: the tocilizumab Fab/IL-6R complex
Components
  • Complex: the tocilizumab Fab/IL-6R complex
    • Protein or peptide: Heavy chain of Tocilizumab Fab
    • Protein or peptide: Light chain of Tocilizumab Fab
    • Protein or peptide: Interleukin-6 receptor subunit alpha
    • Protein or peptide: IL6R-D2 peptide
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

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Supramolecule #1: the tocilizumab Fab/IL-6R complex

SupramoleculeName: the tocilizumab Fab/IL-6R complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Heavy chain of Tocilizumab Fab

MacromoleculeName: Heavy chain of Tocilizumab Fab / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 24.12508 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: QVQLQESGPG LVRPSQTLSL TCTVSGYSIT SDHAWSWVRQ PPGRGLEWIG YISYSGITTY NPSLKSRVTM LRDTSKNQFS LRLSSVTAA DTAVYYCARS LARTTAMDYW GQGSLVTVSS ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS W NSGALTSG ...String:
QVQLQESGPG LVRPSQTLSL TCTVSGYSIT SDHAWSWVRQ PPGRGLEWIG YISYSGITTY NPSLKSRVTM LRDTSKNQFS LRLSSVTAA DTAVYYCARS LARTTAMDYW GQGSLVTVSS ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS W NSGALTSG VHTFPAVLQS SGLYSLSSVV TVPSSSLGTQ TYICNVNHKP SNTKVDKKVE PKSCDKTH

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Macromolecule #2: Light chain of Tocilizumab Fab

MacromoleculeName: Light chain of Tocilizumab Fab / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 23.527078 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: DIQMTQSPSS LSASVGDRVT ITCRASQDIS SYLNWYQQKP GKAPKLLIYY TSRLHSGVPS RFSGSGSGTD FTFTISSLQP EDIATYYCQ QGNTLPYTFG QGTKVEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS ...String:
DIQMTQSPSS LSASVGDRVT ITCRASQDIS SYLNWYQQKP GKAPKLLIYY TSRLHSGVPS RFSGSGSGTD FTFTISSLQP EDIATYYCQ QGNTLPYTFG QGTKVEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS KDSTYSLSST LTLSKADYEK HKVYACEVTH QGLSSPVTKS FNRGEC

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Macromolecule #3: Interleukin-6 receptor subunit alpha

MacromoleculeName: Interleukin-6 receptor subunit alpha / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 40.283441 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MLAVGCALLA ALLAAPGAAL APRRCPAQEV ARGVLTSLPG DSVTLTCPGV EPEDNATVHW VLRKPAAGSH PSRWAGMGRR LLLRSVQLH DSGNYSCYRA GRPAGTVHLL VDVPPEEPQL SCFRKSPLSN VVCEWGPRST PSLTTKAVLL VRKFQNSPAE D FQEPCQYS ...String:
MLAVGCALLA ALLAAPGAAL APRRCPAQEV ARGVLTSLPG DSVTLTCPGV EPEDNATVHW VLRKPAAGSH PSRWAGMGRR LLLRSVQLH DSGNYSCYRA GRPAGTVHLL VDVPPEEPQL SCFRKSPLSN VVCEWGPRST PSLTTKAVLL VRKFQNSPAE D FQEPCQYS QESQKFSCQL AVPEGDSSFY IVSMCVASSV GSKFSKTQTF QGCGILQPDP PANITVTAVA RNPRWLSVTW QD PHSWNSS FYRLRFELRY RAERSKTFTT WMVKDLQHHC VIHDAWSGLR HVVQLRAQEE FGQGEWSEWS PEAMGTPWTE SRS PPAENE VSTPMQALTT NKDDDNILFR DSANATSLPG SRRRGSCGL

UniProtKB: Interleukin-6 receptor subunit alpha

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Macromolecule #4: IL6R-D2 peptide

MacromoleculeName: IL6R-D2 peptide / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 1.148355 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
FRKSPLSNVV

UniProtKB: Interleukin-6 receptor subunit alpha

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Macromolecule #5: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 5 / Number of copies: 1 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 8
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2.7 µm / Nominal defocus min: 1.4000000000000001 µm
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 55.0 e/Å2

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Image processing

Startup modelType of model: OTHER
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 351599

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