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- EMDB-41367: Structure of the IL-5 Signaling Complex -

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Basic information

Entry
Database: EMDB / ID: EMD-41367
TitleStructure of the IL-5 Signaling Complex
Map data
Sample
  • Complex: IL-5 Receptor Complex
    • Protein or peptide: Cytokine receptor common subunit beta
    • Protein or peptide: Interleukin-5
    • Protein or peptide: Interleukin-5 receptor subunit alpha
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
KeywordsIL-5 / cytokine / receptor / SIGNALING PROTEIN
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)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.6 Å
AuthorsCaveney NA / Garcia KC
Funding support United States, 1 items
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, 2023-
Header (metadata) releaseApr 10, 2024-
Map releaseApr 10, 2024-
UpdateMay 28, 2025-
Current statusMay 28, 2025Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_41367.png

Downloads & links

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Map

FileDownload / File: emd_41367.map.gz / Format: CCP4 / Size: 20.8 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
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AxesZ (Sec.)Y (Row.)X (Col.)
1.31 Å/pix.
x 176 pix.
= 229.856 Å		1.31 Å/pix.
x 176 pix.
= 229.856 Å		1.31 Å/pix.
x 176 pix.
= 229.856 Å

Surface

Projections

Slices (1/3)

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Images are generated by Spider.

Voxel sizeX=Y=Z: 1.306 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.126
Minimum - Maximum-0.023213824 - 2.277234
Average (Standard dev.)0.0013444866 (±0.026384734)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions176176176
Spacing176176176
CellA=B=C: 229.856 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_41367_msk_1.map
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Histogram

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Half map: #1

Fileemd_41367_half_map_1.map
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Half map: #2

Fileemd_41367_half_map_2.map
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Sample components

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Entire : IL-5 Receptor Complex

EntireName: IL-5 Receptor Complex
Components
  • Complex: IL-5 Receptor Complex
    • Protein or peptide: Cytokine receptor common subunit beta
    • Protein or peptide: Interleukin-5
    • Protein or peptide: Interleukin-5 receptor subunit alpha
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

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Supramolecule #1: IL-5 Receptor Complex

SupramoleculeName: IL-5 Receptor Complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Cytokine receptor common subunit beta

MacromoleculeName: Cytokine receptor common subunit beta / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 81.07875 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: DYKDDDDKMV SKGEELFTGV VPILVELDGD VNGHKFSVSG EGEGDATYGK LTLKFICTTG KLPVPWPTLV TTLTYGVQCF SRYPDHMKQ HDFFKSAMPE GYVQERTIFF KDDGNYKTRA EVKFEGDTLV NRIELKGIDF KEDGNILGHK LEYNYNSHNV Y IMADKQKN ...String:
DYKDDDDKMV SKGEELFTGV VPILVELDGD VNGHKFSVSG EGEGDATYGK LTLKFICTTG KLPVPWPTLV TTLTYGVQCF SRYPDHMKQ HDFFKSAMPE GYVQERTIFF KDDGNYKTRA EVKFEGDTLV NRIELKGIDF KEDGNILGHK LEYNYNSHNV Y IMADKQKN GIKVNFKIRH NIEDGSVQLA DHYQQNTPIG DGPVLLPDNH YLSTQSALSK DPNEKRDHMV LLEFVTAAGI TL GMDELYK LEVLFQGPGS GAEETIPLQT LRCYNDYTSH ITCRWADTQD AQRLVNVTLI RRVNEDLLEP VSCDLSDDMP WSA CPHPRC VPRRCVIPCQ SFVVTDVDYF SFQPDRPLGT RLTVTLTQHV QPPEPRDLQI STDQDHFLLT WSVALGSPQS HWLS PGDLE FEVVYKRLQD SWEDAAILLS NTSQATLGPE HLMPSSTYVA RVRTRLAPGS RLSGRPSKWS PEVCWDSQPG DEAQP QNLE CFFDGAAVLS CSWEVRKEVA SSVSFGLFYK PSPDAGEEEC SPVLREGLGS LHTRHHCQIP VPDPATHGQY IVSVQP RRA EKHIKSSVNI QMAPPSLNVT KDGDSYSLRW ETMKMRYEHI DHTFEIQYRK DTATWKDSKT ETLQNAHSMA LPALEPS TR YWARVRVRTS RTGYNGIWSE WSEARSWDTE SVLPMGGGGS TTAPSAQLEK ELQALEKENA QLEWELQALE KELAQ

UniProtKB: Cytokine receptor common subunit beta

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Macromolecule #2: Interleukin-5

MacromoleculeName: Interleukin-5 / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 16.836051 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
DYKDDDDKIP TEIPTSALVK ETLALLSTHR TLLIANETLR IPVPVHKNHQ LCTEEIFQGI GTLESQTVQG GTVERLFKNL SLIKKYIDG QKKKCGEERR RVNQFLDYLQ EFLGVMNTEW IIESGAAEDQ VDPRLIDGKH HHHHHHH

UniProtKB: Interleukin-5

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Macromolecule #3: Interleukin-5 receptor subunit alpha

MacromoleculeName: Interleukin-5 receptor subunit alpha / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 44.590176 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: DYKDDDDKDL LPDEKISLLP PVNFTIKVTG LAQVLLQWKP NPDQEQRNVN LEYQVKINAP KEDDYETRIT ESKCVTILHK GFSASVRTI LQNDHSLLAS SWASAELHAP PGSPGTSIVN LTCTTNTTED NYSRLRSYQV SLHCTWLVGT DAPEDTQYFL Y YRYGSWTE ...String:
DYKDDDDKDL LPDEKISLLP PVNFTIKVTG LAQVLLQWKP NPDQEQRNVN LEYQVKINAP KEDDYETRIT ESKCVTILHK GFSASVRTI LQNDHSLLAS SWASAELHAP PGSPGTSIVN LTCTTNTTED NYSRLRSYQV SLHCTWLVGT DAPEDTQYFL Y YRYGSWTE ECQEYSKDTL GRNIACWFPR TFILSKGRDW LAVLVNGSSK HSAIRPFDQL FALHAIDQIN PPLNVTAEIE GT RLSIQWE KPVSAFPIHC FDYEVKIHNT RNGYLQIEKL MTNAFISIID DLSKYDVQVR AAVSSMCREA GLWSEWSQPI YVG NDEHKP LREGGGGSTT APSAQLKKKL QALKKKNAQL KWKLQALKKK LAQGAAEDQV DPRLIDGKHH HHHHHH

UniProtKB: Interleukin-5 receptor subunit alpha

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Macromolecule #4: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 4 / Number of copies: 5 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

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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 KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 59.9 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: OTHER / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.8 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: OTHER
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 4) / Number images used: 418819
Initial angle assignmentType: OTHER
Final angle assignmentType: OTHER
FSC plot (resolution estimation)

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