[English] 日本語
Yorodumi
- PDB-8ywq: Crystal structure of the Fab fragment of the anti-IL-6 antibody I... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8ywq
TitleCrystal structure of the Fab fragment of the anti-IL-6 antibody I9H in complex with a domain-swapped IL-6 dimer
Components
  • Heavy chain of the Fab fragment of anti-IL-6 antibody I9H
  • Interleukin-6
  • Light chain of the Fab fragment of anti-IL-6 antibody I9H
KeywordsIMMUNE SYSTEM / interleukin / dimer / swap
Function / homology
Function and homology information


regulation of astrocyte activation / glucagon secretion / positive regulation of interleukin-21 production / 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 / germinal center B cell differentiation / interleukin-6 receptor complex ...regulation of astrocyte activation / glucagon secretion / positive regulation of interleukin-21 production / 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 / germinal center B cell differentiation / interleukin-6 receptor complex / positive regulation of type B pancreatic cell apoptotic process / positive regulation of apoptotic DNA fragmentation / hepatocyte proliferation / positive regulation of extracellular matrix disassembly / regulation of microglial cell activation / response to peptidoglycan / neutrophil apoptotic process / interleukin-6 receptor binding / positive regulation of B cell activation / positive regulation of receptor signaling pathway via STAT / inflammatory response to wounding / T-helper 17 cell lineage commitment / positive regulation of T-helper 2 cell cytokine production / negative regulation of collagen biosynthetic process / endocrine pancreas development / positive regulation of acute inflammatory response / regulation of neuroinflammatory response / vascular endothelial growth factor production / positive regulation of neuroinflammatory response / T follicular helper cell differentiation / negative regulation of chemokine production / positive regulation of leukocyte chemotaxis / positive regulation of platelet aggregation / neutrophil mediated immunity / positive regulation of cytokine production involved in inflammatory response / cell surface receptor signaling pathway via STAT / negative regulation of bone resorption / positive regulation of leukocyte adhesion to vascular endothelial cell / CD163 mediating an anti-inflammatory response / Interleukin-6 signaling / positive regulation of peptidyl-tyrosine phosphorylation / positive regulation of immunoglobulin production / MAPK3 (ERK1) activation / interleukin-6-mediated signaling pathway / maintenance of blood-brain barrier / negative regulation of fat cell differentiation / MAPK1 (ERK2) activation / Interleukin-10 signaling / positive regulation of interleukin-17 production / monocyte chemotaxis / humoral immune response / positive regulation of interleukin-10 production / Transcriptional Regulation by VENTX / negative regulation of lipid storage / positive regulation of vascular endothelial growth factor production / cell surface receptor signaling pathway via JAK-STAT / regulation of angiogenesis / positive regulation of osteoblast differentiation / positive regulation of epithelial to mesenchymal transition / response to glucocorticoid / positive regulation of T cell proliferation / positive regulation of chemokine production / positive regulation of peptidyl-serine phosphorylation / positive regulation of glial cell proliferation / regulation of insulin secretion / positive regulation of DNA-binding transcription factor activity / liver regeneration / positive regulation of interleukin-1 beta production / positive regulation of translation / cytokine activity / acute-phase response / response to activity / positive regulation of interleukin-8 production / positive regulation of receptor signaling pathway via JAK-STAT / Post-translational protein phosphorylation / positive regulation of smooth muscle cell proliferation / growth factor activity / cytokine-mediated signaling pathway / cellular response to virus / platelet activation / positive regulation of miRNA transcription / negative regulation of neurogenesis / positive regulation of interleukin-6 production / cellular response to hydrogen peroxide / neuron cellular homeostasis / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / neuron projection development / positive regulation of tumor necrosis factor production / ADORA2B mediated anti-inflammatory cytokines production / glucose homeostasis / cellular response to lipopolysaccharide / Senescence-Associated Secretory Phenotype (SASP) / defense response to Gram-negative bacterium / Interleukin-4 and Interleukin-13 signaling / defense response to virus / positive regulation of MAPK cascade / defense response to Gram-positive bacterium / positive regulation of apoptotic process / inflammatory response / endoplasmic reticulum lumen
Similarity search - Function
Interleukin-6 / Interleukin-6/G-CSF/MGF family / Interleukin-6/GCSF/MGF, conserved site / Interleukin-6 / G-CSF / MGF signature. / Interleukin-6/GCSF/MGF / Interleukin-6 homologues / Four-helical cytokine-like, core
Similarity search - Domain/homology
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.51 Å
AuthorsBukhdruker, S. / Yudenko, A. / Marin, E. / Remeeva, A. / Rodin, S. / Burtseva, A. / Petrov, A. / Ischenko, A. / Borshchevskiy, V.
Funding support Russian Federation, 1items
OrganizationGrant numberCountry
Ministry of Education and Science of the Russian Federation075-15-2021-1354 Russian Federation
CitationJournal: Structure / Year: 2025
Title: Structural basis of signaling complex inhibition by IL-6 domain-swapped dimers.
Authors: Yudenko, A. / Bukhdruker, S. / Shishkin, P. / Rodin, S. / Burtseva, A. / Petrov, A. / Pigareva, N. / Sokolov, A. / Zinovev, E. / Eliseev, I. / Remeeva, A. / Marin, E. / Mishin, A. / ...Authors: Yudenko, A. / Bukhdruker, S. / Shishkin, P. / Rodin, S. / Burtseva, A. / Petrov, A. / Pigareva, N. / Sokolov, A. / Zinovev, E. / Eliseev, I. / Remeeva, A. / Marin, E. / Mishin, A. / Gordeliy, V. / Gushchin, I. / Ischenko, A. / Borshchevskiy, V.
History
DepositionMar 31, 2024Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Nov 6, 2024Provider: repository / Type: Initial release
Revision 1.1Dec 4, 2024Group: Database references / Category: citation / citation_author
Item: _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed ..._citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _citation_author.name
Revision 1.2Jan 15, 2025Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.year

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
H: Heavy chain of the Fab fragment of anti-IL-6 antibody I9H
L: Light chain of the Fab fragment of anti-IL-6 antibody I9H
A: Interleukin-6
hetero molecules


Theoretical massNumber of molelcules
Total (without water)69,3394
Polymers69,3153
Non-polymers241
Water543
1
H: Heavy chain of the Fab fragment of anti-IL-6 antibody I9H
L: Light chain of the Fab fragment of anti-IL-6 antibody I9H
A: Interleukin-6
hetero molecules

H: Heavy chain of the Fab fragment of anti-IL-6 antibody I9H
L: Light chain of the Fab fragment of anti-IL-6 antibody I9H
A: Interleukin-6
hetero molecules


Theoretical massNumber of molelcules
Total (without water)138,6798
Polymers138,6306
Non-polymers492
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation2_555-x,-y,z1
Unit cell
Length a, b, c (Å)126.621, 151.875, 76.053
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number21
Space group name H-MC222
Space group name HallC22
Symmetry operation#1: x,y,z
#2: x,-y,-z
#3: -x,y,-z
#4: -x,-y,z
#5: x+1/2,y+1/2,z
#6: x+1/2,-y+1/2,-z
#7: -x+1/2,y+1/2,-z
#8: -x+1/2,-y+1/2,z
Components on special symmetry positions
IDModelComponents
11A-501-

MG

21A-602-

HOH

31A-603-

HOH

-
Components

#1: Antibody Heavy chain of the Fab fragment of anti-IL-6 antibody I9H


Mass: 24912.051 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Cricetulus griseus (Chinese hamster) / Strain (production host): CHO-IL69hum
#2: Antibody Light chain of the Fab fragment of anti-IL-6 antibody I9H


Mass: 23396.971 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Cricetulus griseus (Chinese hamster) / Strain (production host): CHO-IL69hum
#3: Protein Interleukin-6 / IL-6 / B-cell stimulatory factor 2 / BSF-2 / CTL differentiation factor / CDF / Hybridoma growth ...IL-6 / B-cell stimulatory factor 2 / BSF-2 / CTL differentiation factor / CDF / Hybridoma growth factor / Interferon beta-2 / IFN-beta-2


Mass: 21005.961 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: IL6, IFNB2 / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: P05231
#4: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Mg
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 3 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestN
Has protein modificationY

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 2.63 Å3/Da / Density % sol: 53.28 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 10.5
Details: 40% v/v 2-methyl-2,4-pentanediol, 100 mM CAPS (seed stock crystallization conditions: 14-16% PEG 8000, 100 mM magnesium acetate, 100 mM MES pH 6.5)

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 0.85 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Nov 19, 2019
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.85 Å / Relative weight: 1
ReflectionResolution: 2.51→40.97 Å / Num. obs: 14890 / % possible obs: 91.7 % / Redundancy: 13 % / Biso Wilson estimate: 89.68 Å2 / CC1/2: 0.999 / Rpim(I) all: 0.031 / Net I/σ(I): 11.2
Reflection shellResolution: 2.51→2.82 Å / Redundancy: 12.3 % / Mean I/σ(I) obs: 0.7 / Num. unique obs: 744 / CC1/2: 0.098 / Rpim(I) all: 1.411 / % possible all: 69.3

-
Processing

Software
NameVersionClassification
XDS20190315data reduction
STARANISO2.3.15data scaling
PHASER2.8.3phasing
PHENIX1.20.1_4487refinement
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1ALU,8YWP

1alu

8ywp


Resolution: 2.51→40.97 Å / SU ML: 0.3274 / Cross valid method: FREE R-VALUE / σ(F): 1.33 / Phase error: 40.8304
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2774 1476 9.95 %
Rwork0.2394 13357 -
obs0.2432 14833 58.19 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 89.35 Å2
Refinement stepCycle: LAST / Resolution: 2.51→40.97 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4267 0 1 3 4271
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00184358
X-RAY DIFFRACTIONf_angle_d0.50835964
X-RAY DIFFRACTIONf_chiral_restr0.0396709
X-RAY DIFFRACTIONf_plane_restr0.0042762
X-RAY DIFFRACTIONf_dihedral_angle_d11.43011488
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.51-2.590.581970.478466X-RAY DIFFRACTION3.22
2.59-2.680.5314250.4848188X-RAY DIFFRACTION9.45
2.68-2.790.4928370.4927300X-RAY DIFFRACTION14.8
2.79-2.920.3445460.3986474X-RAY DIFFRACTION22.73
2.92-3.070.3713780.3807732X-RAY DIFFRACTION35.22
3.07-3.260.43781260.37861195X-RAY DIFFRACTION57.86
3.26-3.520.38812160.34511941X-RAY DIFFRACTION93.26
3.52-3.870.30212290.27392052X-RAY DIFFRACTION99.09
3.87-4.430.28772370.22472090X-RAY DIFFRACTION99.96
4.43-5.580.23862320.20632116X-RAY DIFFRACTION99.96
5.58-40.970.23812430.20382203X-RAY DIFFRACTION99.15
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
11.062012057870.4877016250830.5883319529681.099751320560.9417013450842.19498917260.3843298238030.549722195222-0.403456778654-0.3527753205180.386430285456-0.316762450535-0.05135564312440.1889996136662.100260181210.363500864802-0.153683674677-0.286914570110.157426276793-0.2307464065630.258940975725-26.3534020568-20.666676001329.7318912311
20.8175513693250.161853616020.04828931153191.032207753510.07691273787640.3676460558680.173797097566-0.32015970918-0.166640779374-0.0256223101336-0.1405239452140.143029137536-0.0375608126131-0.855979141939-4.81735788323E-50.449597315974-0.0567398089341-0.09209712940910.8685143134120.009355039326920.460088489264-43.581003264-19.840104661936.7376925256
31.485482038010.236302297120.4846799011940.748496821365-0.1543764927892.059302356830.4872149904850.181828520009-0.2037410117040.2434244146810.200758650030.004953617519320.171125182712-0.1159310142790.9071475069440.3376633902530.0489904332561-0.00898518337880.213477146353-0.03560815685790.366643760953-1.82236941127-1.2168791146463.1008095693
Refinement TLS group

Refine-ID: X-RAY DIFFRACTION

IDRefine TLS-IDSelection detailsAuth asym-IDLabel asym-IDAuth seq-IDLabel seq-ID
11(chain 'H' and resid 1 through 225)HA1 - 2251 - 218
22(chain 'L' and resid 1 through 213)LB1 - 2131 - 213
33(chain 'A' and resid 19 through 184)AC19 - 1841 - 148

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more