[English] 日本語
Yorodumi
- PDB-8qy4: Structure of interleukin 11 (gp130 P496L mutant). -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8qy4
TitleStructure of interleukin 11 (gp130 P496L mutant).
Components
  • Interleukin-11
  • Interleukin-11 receptor subunit alpha
  • Interleukin-6 receptor subunit beta
KeywordsIMMUNE SYSTEM / interleukin / gp130
Function / homology
Function and homology information


interleukin-11 receptor binding / oncostatin-M receptor activity / IL-6-type cytokine receptor ligand interactions / MAPK3 (ERK1) activation / MAPK1 (ERK2) activation / Interleukin-27 signaling / leukemia inhibitory factor receptor activity / interleukin-6 receptor activity / interleukin-6 binding / Interleukin-6 signaling ...interleukin-11 receptor binding / oncostatin-M receptor activity / IL-6-type cytokine receptor ligand interactions / MAPK3 (ERK1) activation / MAPK1 (ERK2) activation / Interleukin-27 signaling / leukemia inhibitory factor receptor activity / interleukin-6 receptor activity / interleukin-6 binding / Interleukin-6 signaling / Interleukin-35 Signalling / oncostatin-M receptor complex / ciliary neurotrophic factor receptor binding / interleukin-11 receptor activity / interleukin-11 binding / ciliary neurotrophic factor receptor complex / interleukin-6 receptor complex / megakaryocyte differentiation / interleukin-27-mediated signaling pathway / head development / negative regulation of hormone secretion / interleukin-6 receptor binding / interleukin-11-mediated signaling pathway / regulation of Notch signaling pathway / developmental process / positive regulation of astrocyte differentiation / intestinal epithelial cell development / IL-6-type cytokine receptor ligand interactions / cell surface receptor signaling pathway via STAT / positive regulation of peptidyl-tyrosine phosphorylation / glycogen metabolic process / interleukin-6-mediated signaling pathway / positive regulation of Notch signaling pathway / fat cell differentiation / protein tyrosine kinase activator activity / positive regulation of osteoblast differentiation / positive regulation of T cell proliferation / coreceptor activity / positive regulation of peptidyl-serine phosphorylation / B cell differentiation / cytokine activity / growth factor activity / cytokine-mediated signaling pathway / transmembrane signaling receptor activity / cell body / scaffold protein binding / negative regulation of neuron apoptotic process / cell population proliferation / receptor complex / positive regulation of MAPK cascade / membrane raft / external side of plasma membrane / neuronal cell body / positive regulation of cell population proliferation / dendrite / signal transduction / positive regulation of transcription by RNA polymerase II / extracellular space / extracellular region / identical protein binding / plasma membrane / cytoplasm
Similarity search - Function
Interleukin-11, mammalian / Interleukin-11 / Interleukin 11 / : / : / Type I cytokine receptor, cytokine-binding domain / Long hematopoietin receptor, soluble alpha chain, conserved site / Long hematopoietin receptor, soluble alpha chains family signature. / Interleukin-6 receptor alpha chain, binding / Immunoglobulin C2-set-like, ligand-binding ...Interleukin-11, mammalian / Interleukin-11 / Interleukin 11 / : / : / Type I cytokine receptor, cytokine-binding domain / Long hematopoietin receptor, soluble alpha chain, conserved site / Long hematopoietin receptor, soluble alpha chains family signature. / Interleukin-6 receptor alpha chain, binding / Immunoglobulin C2-set-like, ligand-binding / Ig-like C2-type domain / Long hematopoietin receptor, Gp130 family 2, conserved site / Long hematopoietin receptor, gp130 family signature. / Four-helical cytokine-like, core / Fibronectin type III domain / Fibronectin type 3 domain / 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-11 / Interleukin-6 receptor subunit beta / Interleukin-11 receptor subunit alpha
Similarity search - Component
Biological speciesHomo sapiens (human)
Mus musculus (house mouse)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.06 Å
AuthorsGardner, S. / Bubeck, D. / Jin, Y.
Funding support United Kingdom, European Union, 4items
OrganizationGrant numberCountry
Wellcome Trust202323/Z/16 United Kingdom
European Research Council (ERC)C-206-STGEuropean Union
Engineering and Physical Sciences Research CouncilEP/X035603/1 United Kingdom
Biotechnology and Biological Sciences Research Council (BBSRC)BB/M011178/1 United Kingdom
Citation
Journal: Nat Commun / Year: 2024
Title: Structural insights into IL-11-mediated signalling and human IL6ST variant-associated immunodeficiency.
Authors: Scott Gardner / Yibo Jin / Paul K Fyfe / Tomas B Voisin / Junel Sotolongo Bellón / Elizabeth Pohler / Jacob Piehler / Ignacio Moraga / Doryen Bubeck /
Abstract: IL-11 and IL-6 activate signalling via assembly of the cell surface receptor gp130; however, it is unclear how signals are transmitted across the membrane to instruct cellular responses. Here we ...IL-11 and IL-6 activate signalling via assembly of the cell surface receptor gp130; however, it is unclear how signals are transmitted across the membrane to instruct cellular responses. Here we solve the cryoEM structure of the IL-11 receptor recognition complex to discover how differences in gp130-binding interfaces may drive signalling outcomes. We explore how mutations in the IL6ST gene encoding for gp130, which cause severe immune deficiencies in humans, impair signalling without blocking cytokine binding. We use cryoEM to solve structures of both IL-11 and IL-6 complexes with a mutant form of gp130 associated with human disease. Together with molecular dynamics simulations, we show that the disease-associated variant led to an increase in flexibility including motion within the cytokine-binding core and increased distance between extracellular domains. However, these distances are minimized as the transmembrane helix exits the membrane, suggesting a stringency in geometry for signalling and dimmer switch mode of action.
#1: Journal: Acta Crystallogr D Struct Biol / Year: 2019
Title: Macromolecular structure determination using X-rays, neutrons and electrons: recent developments in Phenix.
Authors: Dorothee Liebschner / Pavel V Afonine / Matthew L Baker / Gábor Bunkóczi / Vincent B Chen / Tristan I Croll / Bradley Hintze / Li Wei Hung / Swati Jain / Airlie J McCoy / Nigel W Moriarty ...Authors: Dorothee Liebschner / Pavel V Afonine / Matthew L Baker / Gábor Bunkóczi / Vincent B Chen / Tristan I Croll / Bradley Hintze / Li Wei Hung / Swati Jain / Airlie J McCoy / Nigel W Moriarty / Robert D Oeffner / Billy K Poon / Michael G Prisant / Randy J Read / Jane S Richardson / David C Richardson / Massimo D Sammito / Oleg V Sobolev / Duncan H Stockwell / Thomas C Terwilliger / Alexandre G Urzhumtsev / Lizbeth L Videau / Christopher J Williams / Paul D Adams /
Abstract: Diffraction (X-ray, neutron and electron) and electron cryo-microscopy are powerful methods to determine three-dimensional macromolecular structures, which are required to understand biological ...Diffraction (X-ray, neutron and electron) and electron cryo-microscopy are powerful methods to determine three-dimensional macromolecular structures, which are required to understand biological processes and to develop new therapeutics against diseases. The overall structure-solution workflow is similar for these techniques, but nuances exist because the properties of the reduced experimental data are different. Software tools for structure determination should therefore be tailored for each method. Phenix is a comprehensive software package for macromolecular structure determination that handles data from any of these techniques. Tasks performed with Phenix include data-quality assessment, map improvement, model building, the validation/rebuilding/refinement cycle and deposition. Each tool caters to the type of experimental data. The design of Phenix emphasizes the automation of procedures, where possible, to minimize repetitive and time-consuming manual tasks, while default parameters are chosen to encourage best practice. A graphical user interface provides access to many command-line features of Phenix and streamlines the transition between programs, project tracking and re-running of previous tasks.
History
DepositionOct 25, 2023Deposition site: PDBE / Processing site: PDBE
Revision 1.0Feb 21, 2024Provider: repository / Type: Initial release
Revision 1.1Sep 4, 2024Group: Data collection / Database references / Category: citation / citation_author / em_admin
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _em_admin.last_update
Revision 1.2Nov 13, 2024Group: Data collection / Structure summary
Category: em_admin / pdbx_entry_details / pdbx_modification_feature
Item: _em_admin.last_update / _pdbx_entry_details.has_protein_modification

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Interleukin-11
C: Interleukin-6 receptor subunit beta
D: Interleukin-11
F: Interleukin-6 receptor subunit beta
B: Interleukin-11 receptor subunit alpha
E: Interleukin-11 receptor subunit alpha
hetero molecules


Theoretical massNumber of molelcules
Total (without water)343,33922
Polymers338,5806
Non-polymers4,75816
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
d_1ens_1chain "A"
d_2ens_1chain "D"
d_1ens_2chain "B"
d_2ens_2chain "E"
d_1ens_3chain "C"
d_2ens_3chain "F"

NCS domain segments:
Dom-IDComponent-IDEns-IDBeg auth comp-IDBeg label comp-IDEnd auth comp-IDEnd label comp-IDAuth asym-IDLabel asym-IDAuth seq-IDLabel seq-ID
d_11ens_1PROPROLEULEUAA35 - 19935 - 199
d_21ens_1PROPROLEULEUDC35 - 19935 - 199
d_11ens_2PROPROTHRTHRBE112 - 317112 - 317
d_12ens_2NAGNAGNAGNAGII1
d_13ens_2NAGNAGNAGNAGII2
d_14ens_2NAGNAGNAGNAGJJ1
d_15ens_2NAGNAGNAGNAGJJ2
d_21ens_2PROPROTHRTHREF112 - 317112 - 317
d_22ens_2NAGNAGNAGNAGKK1
d_23ens_2NAGNAGNAGNAGKK2
d_24ens_2NAGNAGNAGNAGLL1
d_25ens_2NAGNAGNAGNAGLL2
d_11ens_3LEULEUTHRTHRCB25 - 60725 - 607
d_12ens_3NAGNAGNAGNAGGG1
d_13ens_3NAGNAGNAGNAGGG2
d_14ens_3NAGNAGNAGNAGCM1001
d_15ens_3NAGNAGNAGNAGCN1002
d_16ens_3NAGNAGNAGNAGCO1003
d_17ens_3NAGNAGNAGNAGCP1004
d_18ens_3NAGNAGNAGNAGCQ1005
d_21ens_3LEULEUTHRTHRFD25 - 60725 - 607
d_22ens_3NAGNAGNAGNAGHH1
d_23ens_3NAGNAGNAGNAGHH2
d_24ens_3NAGNAGNAGNAGFR1001
d_25ens_3NAGNAGNAGNAGFS1002
d_26ens_3NAGNAGNAGNAGFT1003
d_27ens_3NAGNAGNAGNAGFU1004
d_28ens_3NAGNAGNAGNAGFV1005

NCS ensembles :
ID
ens_1
ens_2
ens_3

NCS oper:
IDCodeMatrixVector
1given(-0.999990008453, 0.00439868322267, -0.000796605286919), (-0.0043970034382, -0.99998813169, -0.00209829437618), (-0.000805825564829, -0.00209477073479, 0.999997481287)473.868467771, 476.355191676, 0.734085733312
2given(-0.99997905264, -0.00589651779862, -0.00266933699387), (0.00587692794244, -0.99995617134, 0.00728814903376), (-0.00271219470091, 0.00727230886511, 0.999969878308)477.141569233, 471.677519603, -1.3264822899
3given(-0.999997965158, 0.00154926137421, -0.00129207897269), (-0.00154924890706, -0.999998799856, -1.06497278327E-5), (-0.00129209392122, -8.64795422592E-6, 0.999999165209)474.826997094, 475.27100001, 0.212740626921

-
Components

#1: Protein Interleukin-11


Mass: 21455.186 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: IL11 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P20809
#2: Protein Interleukin-6 receptor subunit beta


Mass: 102568.906 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Gene: Il6st / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q00560
#3: Protein Interleukin-11 receptor subunit alpha


Mass: 45266.156 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: IL11RA / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q14626
#4: Polysaccharide
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 424.401 Da / Num. of mol.: 6
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DGlcpNAcb1-4DGlcpNAcb1-ROHGlycam Condensed SequenceGMML 1.0
WURCS=2.0/1,2,1/[a2122h-1b_1-5_2*NCC/3=O]/1-1/a4-b1WURCSPDB2Glycan 1.1.0
[][D-1-deoxy-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{}}LINUCSPDB-CARE
#5: Sugar
ChemComp-NAG / 2-acetamido-2-deoxy-beta-D-glucopyranose / N-acetyl-beta-D-glucosamine / 2-acetamido-2-deoxy-beta-D-glucose / 2-acetamido-2-deoxy-D-glucose / 2-acetamido-2-deoxy-glucose / N-ACETYL-D-GLUCOSAMINE


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 10 / Source method: obtained synthetically / Formula: C8H15NO6
IdentifierTypeProgram
DGlcpNAcbCONDENSED IUPAC CARBOHYDRATE SYMBOLGMML 1.0
N-acetyl-b-D-glucopyranosamineCOMMON NAMEGMML 1.0
b-D-GlcpNAcIUPAC CARBOHYDRATE SYMBOLPDB-CARE 1.0
GlcNAcSNFG CARBOHYDRATE SYMBOLGMML 1.0
Has ligand of interestN
Has protein modificationY

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

ComponentName: IL-11 signalling complex / Type: COMPLEX / Entity ID: #1-#3 / Source: RECOMBINANT
Molecular weightExperimental value: NO
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Trichoplusia ni (cabbage looper)
Buffer solutionpH: 7.2
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2250 nm / Nominal defocus min: 500 nm
Image recordingElectron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

-
Processing

EM softwareName: PHENIX / Version: 1.21rc1_4933 / Category: model refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.06 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 487147 / Symmetry type: POINT
RefinementCross valid method: NONE
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
Displacement parametersBiso mean: 41.99 Å2
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.003715534
ELECTRON MICROSCOPYf_angle_d0.870321238
ELECTRON MICROSCOPYf_chiral_restr0.05462454
ELECTRON MICROSCOPYf_plane_restr0.01032684
ELECTRON MICROSCOPYf_dihedral_angle_d12.45595574
Refine LS restraints NCS
Ens-IDDom-IDAsym-IDAuth asym-IDRefine-IDTypeRms dev position (Å)
ens_1d_2AAELECTRON MICROSCOPYNCS constraints8.27248501355E-13
ens_2d_2MCELECTRON MICROSCOPYNCS constraints3.52978435707E-11
ens_3d_2BCELECTRON MICROSCOPYNCS constraints8.7348019437E-12

+
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