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- EMDB-41369: IL-3 Receptor Complex -

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Basic information

Entry
Database: EMDB / ID: EMD-41369
TitleIL-3 Receptor Complex
Map data
Sample
  • Complex: IL-3 Receptor Complex
    • Protein or peptide: IL-3 Receptor Alpha
    • Protein or peptide: Common Beta Receptor
    • Protein or peptide: IL-3
KeywordsIL-3 / cytokine / receptor / SIGNALING PROTEIN
Function / homology
Function and homology information


interleukin-3 receptor activity / interleukin-3 receptor binding / RUNX1 regulates transcription of genes involved in interleukin signaling / Defective CSF2RB causes SMDP5 / Defective CSF2RA causes SMDP4 / 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 ...interleukin-3 receptor activity / interleukin-3 receptor binding / RUNX1 regulates transcription of genes involved in interleukin signaling / Defective CSF2RB causes SMDP5 / Defective CSF2RA causes SMDP4 / 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 / cellular response to interleukin-3 / interleukin-3-mediated signaling pathway / cell surface receptor signaling pathway via STAT / cytokine receptor activity / embryonic hemopoiesis / positive regulation of peptidyl-tyrosine phosphorylation / 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 / cytokine activity / growth factor activity / cytokine-mediated signaling pathway / nervous system development / cell-cell signaling / signaling receptor activity / RAF/MAP kinase cascade / response to lipopolysaccharide / receptor complex / immune response / external side of plasma membrane / positive regulation of cell population proliferation / signal transduction / extracellular space / extracellular region / plasma membrane
Similarity search - Function
Interleukin-3 / Interleukin-3 / IL-3 receptor alpha chain, N-terminal / IL-3 receptor alpha chain N-terminal domain / 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. ...Interleukin-3 / Interleukin-3 / IL-3 receptor alpha chain, N-terminal / IL-3 receptor alpha chain N-terminal domain / 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-3 / Interleukin-3 receptor subunit alpha / Cytokine receptor common subunit beta
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.8 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-
UpdateDec 11, 2024-
Current statusDec 11, 2024Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_41369.png

Downloads & links

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Map

FileDownload / File: emd_41369.map.gz / Format: CCP4 / Size: 25.3 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.)
1.26 Å/pix.
x 188 pix.
= 237.389 Å		1.26 Å/pix.
x 188 pix.
= 237.389 Å		1.26 Å/pix.
x 188 pix.
= 237.389 Å

Surface

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Images are generated by Spider.

Voxel sizeX=Y=Z: 1.26271 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.139
Minimum - Maximum-0.11238886 - 2.0312564
Average (Standard dev.)0.00081038347 (±0.024176195)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions188188188
Spacing188188188
CellA=B=C: 237.38881 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_41369_msk_1.map
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Half map: #2

Fileemd_41369_half_map_1.map
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Half map: #1

Fileemd_41369_half_map_2.map
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Sample components

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Entire : IL-3 Receptor Complex

EntireName: IL-3 Receptor Complex
Components
  • Complex: IL-3 Receptor Complex
    • Protein or peptide: IL-3 Receptor Alpha
    • Protein or peptide: Common Beta Receptor
    • Protein or peptide: IL-3

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Supramolecule #1: IL-3 Receptor Complex

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

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Macromolecule #1: IL-3 Receptor Alpha

MacromoleculeName: IL-3 Receptor Alpha / type: protein_or_peptide / ID: 1 / Enantiomer: LEVO
SequenceString: DYKDDDDKKE DPNPPITNLR MKAKAQQLTW DLNRNVTDIE CVKDADYSMP AVNNSYCQFG AISLCEVTNY TVRVANPPFS TWILFPENSG KPWAGAENLT CWIHDVDFLS CSWAVGPGAP ADVQYDLYLN VANRRQQYEC LHYKTDAQGT RIGCRFDDIS RLSSGSQSSH ...String:
DYKDDDDKKE DPNPPITNLR MKAKAQQLTW DLNRNVTDIE CVKDADYSMP AVNNSYCQFG AISLCEVTNY TVRVANPPFS TWILFPENSG KPWAGAENLT CWIHDVDFLS CSWAVGPGAP ADVQYDLYLN VANRRQQYEC LHYKTDAQGT RIGCRFDDIS RLSSGSQSSH ILVRGRSAAF GIPCTDKFVV FSQIEILTPP NMTAKCNKTH SFMHWKMRSH FNRKFRYELQ IQKRMQPVIT EQVRDRTSFQ LLNPGTYTVQ IRARERVYEF LSAWSTPQRF ECDQEEGANT RAWRTSGGGG STTAPSAQLK KKLQALKKKN AQLKWKLQAL KKKLAQGAAE DQVDPRLIDG KHHHHHHHH

UniProtKB: Interleukin-3 receptor subunit alpha

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Macromolecule #2: Common Beta Receptor

MacromoleculeName: Common Beta Receptor / type: protein_or_peptide / ID: 2 / Enantiomer: LEVO
SequenceString: DYKDDDDKMV SKGEELFTGV VPILVELDGD VNGHKFSVSG EGEGDATYGK LTLKFICTTG KLPVPWPTLV TTLTYGVQCF SRYPDHMKQH DFFKSAMPEG YVQERTIFFK DDGNYKTRAE VKFEGDTLVN RIELKGIDFK EDGNILGHKL EYNYNSHNVY IMADKQKNGI ...String:
DYKDDDDKMV SKGEELFTGV VPILVELDGD VNGHKFSVSG EGEGDATYGK LTLKFICTTG KLPVPWPTLV TTLTYGVQCF SRYPDHMKQH DFFKSAMPEG YVQERTIFFK DDGNYKTRAE VKFEGDTLVN RIELKGIDFK EDGNILGHKL EYNYNSHNVY IMADKQKNGI KVNFKIRHNI EDGSVQLADH YQQNTPIGDG PVLLPDNHYL STQSALSKDP NEKRDHMVLL EFVTAAGITL GMDELYKLEV LFQGPGSGAE ETIPLQTLRC YNDYTSHITC RWADTQDAQR LVNVTLIRRV NEDLLEPVSC DLSDDMPWSA CPHPRCVPRR CVIPCQSFVV TDVDYFSFQP DRPLGTRLTV TLTQHVQPPE PRDLQISTDQ DHFLLTWSVA LGSPQSHWLS PGDLEFEVVY KRLQDSWEDA AILLSNTSQA TLGPEHLMPS STYVARVRTR LAPGSRLSGR PSKWSPEVCW DSQPGDEAQP QNLECFFDGA AVLSCSWEVR KEVASSVSFG LFYKPSPDAG EEECSPVLRE GLGSLHTRHH CQIPVPDPAT HGQYIVSVQP RRAEKHIKSS VNIQMAPPSL NVTKDGDSYS LRWETMKMRY EHIDHTFEIQ YRKDTATWKD SKTETLQNAH SMALPALEPS TRYWARVRVR TSRTGYNGIW SEWSEARSWD TESVLPMGGG GSTTAPSAQL EKELQALEKE NAQLEWELQA LEKELAQ

UniProtKB: Cytokine receptor common subunit beta

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Macromolecule #3: IL-3

MacromoleculeName: IL-3 / type: protein_or_peptide / ID: 3 / Enantiomer: LEVO
SequenceString:
DYKDDDDKAP MTQTTPLKTS WVNCSNMIDE IITHLKQPPL PLLDFNNLNG EDQDILMENN LRRPNLEAFN RAVKSLQNAS AIESILKNLL PCLPLATAAP TRHPIHIKDG DWNEFRRKLT FYLKTLENAQ AQQTTLSLAI FGAAEDQVDP RLIDGKHHHH HHHH

UniProtKB: Interleukin-3

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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

MicroscopeTFS GLACIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 58.8 e/Å2
Electron beamAcceleration voltage: 200 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

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Image processing

Startup modelType of model: OTHER
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.8 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 4) / Number images used: 514634
Initial angle assignmentType: OTHER
Final angle assignmentType: OTHER
FSC plot (resolution estimation)

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