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- PDB-8tld: Structure of the IL-5 Signaling Complex -

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Basic information

Entry
Database: PDB / ID: 8tld
TitleStructure of the IL-5 Signaling Complex
Components
  • Cytokine receptor common subunit beta
  • Interleukin-5
  • Interleukin-5 receptor subunit alpha
KeywordsSIGNALING PROTEIN / IL-5 / cytokine / receptor
Function / homology
Function and homology information


interleukin-5 receptor activity / regulation of interleukin-5 production / positive regulation of eosinophil differentiation / Defective CSF2RB causes SMDP5 / Defective CSF2RA causes SMDP4 / interleukin-5 receptor binding / respiratory gaseous exchange by respiratory system / granulocyte macrophage colony-stimulating factor receptor complex / granulocyte-macrophage colony-stimulating factor signaling pathway / interleukin-5-mediated signaling pathway ...interleukin-5 receptor activity / regulation of interleukin-5 production / positive regulation of eosinophil differentiation / Defective CSF2RB causes SMDP5 / Defective CSF2RA causes SMDP4 / interleukin-5 receptor binding / respiratory gaseous exchange by respiratory system / granulocyte macrophage colony-stimulating factor receptor complex / granulocyte-macrophage colony-stimulating factor signaling pathway / interleukin-5-mediated signaling pathway / positive regulation of leukocyte proliferation / Surfactant metabolism / inflammatory response to antigenic stimulus / cellular response to interleukin-3 / interleukin-3-mediated signaling pathway / cytokine receptor activity / positive regulation of podosome assembly / positive regulation of peptidyl-tyrosine phosphorylation / positive regulation of immunoglobulin production / cytokine binding / immunoglobulin mediated immune response / Interleukin-3, Interleukin-5 and GM-CSF signaling / cell surface receptor signaling pathway via JAK-STAT / Interleukin receptor SHC signaling / coreceptor activity / positive regulation of B cell proliferation / cytokine activity / positive regulation of receptor signaling pathway via JAK-STAT / growth factor activity / cytokine-mediated signaling pathway / signaling receptor activity / RAF/MAP kinase cascade / response to lipopolysaccharide / receptor complex / immune response / inflammatory response / external side of plasma membrane / positive regulation of cell population proliferation / positive regulation of DNA-templated transcription / signal transduction / extracellular space / extracellular region / membrane / plasma membrane
Similarity search - Function
Interleukin-5 / Interleukin 5 / Cytokine IL-3/IL-5/GM-CSF receptor common beta chain / : / GM-CSF/IL-3/IL-5 receptor common beta subunit, N-terminal / Short hematopoietin receptor, family 2, conserved site / Short hematopoietin receptor family 2 signature. / Short hematopoietin receptor family 1 signature. / Type I cytokine receptor, cytokine-binding domain / Interleukin-6 receptor alpha chain, binding ...Interleukin-5 / Interleukin 5 / Cytokine IL-3/IL-5/GM-CSF receptor common beta chain / : / GM-CSF/IL-3/IL-5 receptor common beta subunit, N-terminal / Short hematopoietin receptor, family 2, conserved site / Short hematopoietin receptor family 2 signature. / Short hematopoietin receptor family 1 signature. / Type I cytokine receptor, cytokine-binding domain / Interleukin-6 receptor alpha chain, binding / Short hematopoietin receptor, family 1, conserved site / Four-helical cytokine-like, core / Fibronectin type 3 domain / Fibronectin type-III domain profile. / Fibronectin type III / Fibronectin type III superfamily / Immunoglobulin-like fold
Similarity search - Domain/homology
Interleukin-5 / Cytokine receptor common subunit beta / Interleukin-5 receptor subunit alpha
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.6 Å
AuthorsCaveney, N.A. / Garcia, K.C.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID) United States
CitationJournal: Mol Cell / Year: 2024
Title: Structure of the interleukin-5 receptor complex exemplifies the organizing principle of common beta cytokine signaling.
Authors: Nathanael A Caveney / Grayson E Rodriguez / Christoph Pollmann / Thomas Meyer / Marta T Borowska / Steven C Wilson / Nan Wang / Xinyu Xiang / Karsten D Householder / Pingdong Tao / Leon L Su ...Authors: Nathanael A Caveney / Grayson E Rodriguez / Christoph Pollmann / Thomas Meyer / Marta T Borowska / Steven C Wilson / Nan Wang / Xinyu Xiang / Karsten D Householder / Pingdong Tao / Leon L Su / Robert A Saxton / Jacob Piehler / K Christopher Garcia /
Abstract: Cytokines regulate immune responses by binding to cell surface receptors, including the common subunit beta (βc), which mediates signaling for GM-CSF, IL-3, and IL-5. Despite known roles in ...Cytokines regulate immune responses by binding to cell surface receptors, including the common subunit beta (βc), which mediates signaling for GM-CSF, IL-3, and IL-5. Despite known roles in inflammation, the structural basis of IL-5 receptor activation remains unclear. We present the cryo-EM structure of the human IL-5 ternary receptor complex, revealing architectural principles for IL-5, GM-CSF, and IL-3. In mammalian cell culture, single-molecule imaging confirms hexameric IL-5 complex formation on cell surfaces. Engineered chimeric receptors show that IL-5 signaling, as well as IL-3 and GM-CSF, can occur through receptor heterodimerization, obviating the need for higher-order assemblies of βc dimers. These findings provide insights into IL-5 and βc receptor family signaling mechanisms, aiding in the development of therapies for diseases involving deranged βc signaling.
History
DepositionJul 26, 2023Deposition site: RCSB / Processing site: RCSB
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Revision 1.1Nov 20, 2024Group: Data collection / Structure summary
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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
B: Cytokine receptor common subunit beta
C: Interleukin-5
D: Interleukin-5
E: Cytokine receptor common subunit beta
F: Interleukin-5 receptor subunit alpha
hetero molecules


Theoretical massNumber of molelcules
Total (without water)241,52610
Polymers240,4205
Non-polymers1,1065
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

#1: Protein Cytokine receptor common subunit beta / CDw131 / GM-CSF/IL-3/IL-5 receptor common beta subunit


Mass: 81078.750 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CSF2RB, IL3RB, IL5RB / Production host: Homo sapiens (human) / References: UniProt: P32927
#2: Protein Interleukin-5


Mass: 16836.051 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: IL5 / Production host: Homo sapiens (human) / References: UniProt: P05113
#3: Protein Interleukin-5 receptor subunit alpha


Mass: 44590.176 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: IL5RA / Production host: Homo sapiens (human) / References: UniProt: Q01344
#4: 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.: 5 / 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

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Experimental details

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Experiment

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

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Sample preparation

ComponentName: IL-5 Receptor Complex / Type: COMPLEX / Entity ID: #1-#3 / Source: RECOMBINANT
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 8
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

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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: OTHER / Nominal defocus max: 2000 nm / Nominal defocus min: 800 nm
Image recordingElectron dose: 59.9 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

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Processing

EM software
IDNameVersionCategory
8PHENIXmodel refinement
13cryoSPARC43D reconstruction
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 418819 / Symmetry type: POINT
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.0056116
ELECTRON MICROSCOPYf_angle_d0.6818308
ELECTRON MICROSCOPYf_dihedral_angle_d4.896826
ELECTRON MICROSCOPYf_chiral_restr0.044946
ELECTRON MICROSCOPYf_plane_restr0.0091054

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