[English] 日本語
Yorodumi
- PDB-4o9h: Structure of Interleukin-6 in complex with a Camelid Fab fragment -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4o9h
TitleStructure of Interleukin-6 in complex with a Camelid Fab fragment
Components
  • Heavy Chain of the Camelid Fab fragment 61H7
  • Interleukin-6
  • Light Chain of the Camelid Fab fragment 61H7
KeywordsIMMUNE SYSTEM / IL6: all alpha protein / Fab: all beta protein
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 apoptotic DNA fragmentation / positive regulation of type B pancreatic cell apoptotic process / positive regulation of extracellular matrix disassembly / hepatocyte proliferation / 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 / negative regulation of chemokine production / T follicular helper cell differentiation / positive regulation of neuroinflammatory response / positive regulation of leukocyte chemotaxis / cell surface receptor signaling pathway via STAT / neutrophil mediated immunity / positive regulation of cytokine production involved in inflammatory response / positive regulation of platelet aggregation / 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 signaling / interleukin-6-mediated signaling pathway / maintenance of blood-brain barrier / negative regulation of fat cell differentiation / MAPK3 (ERK1) activation / monocyte chemotaxis / MAPK1 (ERK2) activation / Interleukin-10 signaling / positive regulation of interleukin-17 production / 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 glial cell proliferation / regulation of insulin secretion / liver regeneration / positive regulation of translation / positive regulation of interleukin-1 beta production / cytokine activity / acute-phase response / response to activity / positive regulation of interleukin-8 production / positive regulation of DNA-binding transcription factor activity / positive regulation of receptor signaling pathway via JAK-STAT / positive regulation of smooth muscle cell proliferation / Post-translational protein phosphorylation / growth factor activity / positive regulation of peptidyl-serine phosphorylation / cytokine-mediated signaling pathway / positive regulation of miRNA transcription / platelet activation / negative regulation of neurogenesis / positive regulation of interleukin-6 production / cellular response to virus / cellular response to hydrogen peroxide / neuron cellular homeostasis / neuron projection development / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / positive regulation of peptidyl-tyrosine phosphorylation / ADORA2B mediated anti-inflammatory cytokines production / positive regulation of tumor necrosis factor 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 / Growth Hormone; Chain: A; - #10 / Four-helical cytokine-like, core / Growth Hormone; Chain: A; / Immunoglobulins ...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 / Growth Hormone; Chain: A; - #10 / Four-helical cytokine-like, core / Growth Hormone; Chain: A; / Immunoglobulins / Up-down Bundle / Immunoglobulin-like / Sandwich / Mainly Beta / Mainly Alpha
Similarity search - Domain/homology
Biological speciesHomo sapiens (human)
Llama glama (llama)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.42 Å
AuthorsKlarenbeek, A. / Blanchetot, C. / Schragel, G. / Sadi, A.S. / Ongenae, N. / Hemrika, W. / Wijdenes, J. / Spinelli, S. / Desmyter, A. / Cambillau, C. ...Klarenbeek, A. / Blanchetot, C. / Schragel, G. / Sadi, A.S. / Ongenae, N. / Hemrika, W. / Wijdenes, J. / Spinelli, S. / Desmyter, A. / Cambillau, C. / Hultberg, A. / Kretz-rommel, A. / Dreier, T. / De haard, H.J.W. / Roovers, R.C.
CitationJournal: To be Published
Title: Combining residues of naturally-occurring Camelid somatic affinity variants yields ultra-potent human therapeutic IL-6 antibodies
Authors: Klarenbeek, A. / Blanchetot, C. / Schragel, G. / Sadi, A.S. / Ongenae, N. / Hemrika, W. / Wijdenes, J. / Spinelli, S. / Desmyter, A. / Cambillau, C. / Hultberg, A. / Kretz-Rommel, A. / ...Authors: Klarenbeek, A. / Blanchetot, C. / Schragel, G. / Sadi, A.S. / Ongenae, N. / Hemrika, W. / Wijdenes, J. / Spinelli, S. / Desmyter, A. / Cambillau, C. / Hultberg, A. / Kretz-Rommel, A. / Dreier, T. / De haard, H.J.W. / Roovers, R.C.
History
DepositionJan 2, 2014Deposition site: RCSB / Processing site: PDBJ
Revision 1.0Apr 15, 2015Provider: repository / Type: Initial release
Revision 1.1Apr 29, 2015Group: Other
Revision 1.2Oct 30, 2024Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Structure summary
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_entry_details / pdbx_modification_feature / struct_ref_seq_dif / struct_sheet
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_entry_details.has_protein_modification / _struct_ref_seq_dif.details / _struct_sheet.number_strands

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Interleukin-6
H: Heavy Chain of the Camelid Fab fragment 61H7
L: Light Chain of the Camelid Fab fragment 61H7


Theoretical massNumber of molelcules
Total (without water)67,1713
Polymers67,1713
Non-polymers00
Water5,008278
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)108.210, 47.470, 148.320
Angle α, β, γ (deg.)90.00, 97.00, 90.00
Int Tables number5
Space group name H-MC121

-
Components

#1: 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: 21137.156 Da / Num. of mol.: 1 / Fragment: UNP residues 28-212
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: IL6, IFNB2 / Production host: mammalia (mammals) / References: UniProt: P05231
#2: Antibody Heavy Chain of the Camelid Fab fragment 61H7


Mass: 23504.275 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Llama glama (llama) / Production host: mammalia (mammals)
#3: Antibody Light Chain of the Camelid Fab fragment 61H7


Mass: 22529.770 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Llama glama (llama) / Production host: mammalia (mammals)
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 278 / Source method: isolated from a natural source / Formula: H2O
Has protein modificationY
Sequence detailsIN THIS STRUCTURE, THE SEQUENCES OF THE H AND L CHAINS WERE NOT AVAILABLE AT THE UNIPROT ...IN THIS STRUCTURE, THE SEQUENCES OF THE H AND L CHAINS WERE NOT AVAILABLE AT THE UNIPROT KNOWLEDGEBASE DATABASE (UNIPROTKB) AT THE TIME OF DEPOSITION.

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.81 Å3/Da / Density % sol: 56.3 %
Crystal growTemperature: 277 K / pH: 5.5
Details: 2M Ammonium sulfate, 0.15M Na citrate, pH 5.5, VAPOR DIFFUSION, SITTING DROP, temperature 277K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SOLEIL / Beamline: PROXIMA 1 / Wavelength: 0.98
DetectorType: ADSC QUANTUM 4 / Detector: CCD / Date: Oct 10, 2010
Details: KIRKPATRICK-BAEZ PAIR OF BI- MORPH MIRRORS PLUS CHANNEL CUT CRYOGENICALLY COOLED MONOCHROMATOR CRYSTAL
RadiationMonochromator: KIRKPATRICK-BAEZ PAIR OF BI- MORPH MIRRORS PLUS CHANNEL CUT CRYOGENICALLY COOLED MONOCHROMATOR CRYSTAL
Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.98 Å / Relative weight: 1
ReflectionResolution: 2.42→45 Å / Num. obs: 28984 / % possible obs: 99.5 % / Observed criterion σ(I): 0 / Redundancy: 3.6 % / Biso Wilson estimate: 54.17 Å2 / Rmerge(I) obs: 0.06 / Net I/σ(I): 14.2
Reflection shellResolution: 2.42→2.48 Å / Redundancy: 3.6 % / Rmerge(I) obs: 0.5 / Mean I/σ(I) obs: 2.2 / % possible all: 99.8

-
Processing

Software
NameVersionClassification
ADSCQuantumdata collection
MOLREPphasing
BUSTER2.11.2refinement
XDSdata reduction
XSCALEdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.42→38.65 Å / Cor.coef. Fo:Fc: 0.889 / Cor.coef. Fo:Fc free: 0.862 / SU R Cruickshank DPI: 0.334 / Cross valid method: THROUGHOUT / σ(F): 0 / Stereochemistry target values: Engh & Huber
RfactorNum. reflection% reflectionSelection details
Rfree0.244 1446 5 %RANDOM
Rwork0.216 ---
obs0.217 28918 99.7 %-
all-28918 --
Displacement parametersBiso mean: 65.51 Å2
Baniso -1Baniso -2Baniso -3
1-12.9085 Å20 Å2-4.5705 Å2
2---30.2894 Å20 Å2
3---17.3809 Å2
Refine analyzeLuzzati coordinate error obs: 0.396 Å
Refinement stepCycle: LAST / Resolution: 2.42→38.65 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4207 0 0 278 4485
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.0094301HARMONIC2
X-RAY DIFFRACTIONt_angle_deg1.315853HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d1412SINUSOIDAL2
X-RAY DIFFRACTIONt_incorr_chiral_ct
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_trig_c_planes91HARMONIC2
X-RAY DIFFRACTIONt_gen_planes625HARMONIC5
X-RAY DIFFRACTIONt_it4301HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_omega_torsion3.28
X-RAY DIFFRACTIONt_other_torsion21.19
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_chiral_improper_torsion0582SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact04822SEMIHARMONIC4
LS refinement shellResolution: 2.42→2.5 Å / Total num. of bins used: 15
RfactorNum. reflection% reflection
Rfree0.278 140 5 %
Rwork0.2595 2662 -
all0.2604 2802 -
obs--99.7 %
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)
10.2592-2.03090.61820.0859-1.10310.7313-0.0086-0.01270.0097-0.02090.025-0.003-0.0031-0.0311-0.01640.00360.0817-0.0189-0.00030.03810.0008-30.86623.451115.8987
20.3964-0.57860.08680.5120.21330.3308-0.0102-0.01240.0118-0.01690.01980.01510.0098-0.0209-0.00960.00170.0517-0.0888-0.03770.06020.017-36.436424.37888.792
30.6221-0.5961-0.21310.1626-0.8281.26010.0013-0.0467-0.00120.0123-0.0131-0.00220.0009-0.02430.0118-0.00310.1193-0.01160.05240.0781-0.0716-24.638610.985442.5663
40.29030.2283-0.69560-0.74111.1365-0.00050.0040.01710.00230.0141-0.0139-0.0073-0.0091-0.0136-0.04210.0170.03490.05330.0409-0.0254-4.55541.706364.4494
50.7425-0.9301-0.35560.376-1.24380.3969-0.0017-0.0181-0.0036-0.0147-0.0152-0.00970.03620.01380.01690.00230.14260.0232-0.03730.08570.0303-8.23488.203728.568
61.4278-1.6233-0.44380-0.51010.0001-0.00090.0042-0.01510.00150.0041-0.00380.01110.0023-0.0033-0.03240.05080.05190.04640.0346-0.02086.9903-9.46659.0396
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1{ A|19 - A|92 }
2X-RAY DIFFRACTION2{ A|93 - A|184 }
3X-RAY DIFFRACTION3{ H|1 - H|111 }
4X-RAY DIFFRACTION4{ H|112 - H|220 }
5X-RAY DIFFRACTION5{ L|1 - L|110 }
6X-RAY DIFFRACTION6{ L|111 - L|211 }

+
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