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- EMDB-41368: GM-CSF Receptor Complex -

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Basic information

Entry
Database: EMDB / ID: EMD-41368
TitleGM-CSF Receptor Complex
Map data
Sample
  • Complex: GM-CSF Receptor Complex
    • Protein or peptide: Granulocyte-macrophage colony-stimulating factor receptor subunit alpha
    • Protein or peptide: Cytokine receptor common subunit beta
    • Protein or peptide: Granulocyte-macrophage colony-stimulating factor
KeywordsGM-CSF / cytokine / receptor / SIGNALING PROTEIN
Function / homology
Function and homology information


growth hormone receptor activity / granulocyte macrophage colony-stimulating factor receptor binding / growth hormone receptor complex / histamine secretion / Defective CSF2RB causes SMDP5 / Defective CSF2RA causes SMDP4 / response to silicon dioxide / neutrophil differentiation / epithelial fluid transport / positive regulation of interleukin-23 production ...growth hormone receptor activity / granulocyte macrophage colony-stimulating factor receptor binding / growth hormone receptor complex / histamine secretion / Defective CSF2RB causes SMDP5 / Defective CSF2RA causes SMDP4 / response to silicon dioxide / neutrophil differentiation / epithelial fluid transport / positive regulation of interleukin-23 production / regulation of circadian sleep/wake cycle, sleep / dendritic cell differentiation / respiratory gaseous exchange by respiratory system / granulocyte macrophage colony-stimulating factor receptor complex / granulocyte-macrophage colony-stimulating factor signaling pathway / response to fluid shear stress / myeloid dendritic cell differentiation / interleukin-5-mediated signaling pathway / positive regulation of leukocyte proliferation / Surfactant metabolism / myeloid cell differentiation / cellular response to granulocyte macrophage colony-stimulating factor stimulus / cellular response to interleukin-3 / interleukin-3-mediated signaling pathway / cell surface receptor signaling pathway via STAT / positive regulation of macrophage derived foam cell differentiation / cytokine receptor activity / RUNX1 regulates transcription of genes involved in differentiation of myeloid cells / positive regulation of podosome assembly / growth hormone receptor signaling pathway / Interleukin-10 signaling / cytokine binding / peptide hormone binding / monocyte differentiation / immunoglobulin mediated immune response / macrophage differentiation / Interleukin-3, Interleukin-5 and GM-CSF signaling / negative regulation of extrinsic apoptotic signaling pathway in absence of ligand / cell surface receptor signaling pathway via JAK-STAT / Interleukin receptor SHC signaling / embryonic placenta development / coreceptor activity / cytokine activity / positive regulation of receptor signaling pathway via JAK-STAT / growth factor activity / cytokine-mediated signaling pathway / signaling receptor activity / cellular response to lipopolysaccharide / RAF/MAP kinase cascade / response to lipopolysaccharide / cell population proliferation / immune response / positive regulation of cell migration / external side of plasma membrane / negative regulation of DNA-templated transcription / intracellular membrane-bounded organelle / positive regulation of cell population proliferation / positive regulation of gene expression / signal transduction / extracellular space / extracellular region / plasma membrane / cytosol
Similarity search - Function
IL-3 receptor alpha chain, N-terminal / IL-3 receptor alpha chain N-terminal domain / Granulocyte-macrophage colony-stimulating factor / Cytokine IL-3/IL-5/GM-CSF receptor common beta chain / : / Granulocyte-macrophage colony-stimulating factor / GM-CSF/IL-3/IL-5 receptor common beta subunit, N-terminal / Granulocyte-macrophage colony-stimulating factor signature. / Granulocyte-macrophage colony-simulating factor (GM-CSF) / Short hematopoietin receptor, family 2, conserved site ...IL-3 receptor alpha chain, N-terminal / IL-3 receptor alpha chain N-terminal domain / Granulocyte-macrophage colony-stimulating factor / Cytokine IL-3/IL-5/GM-CSF receptor common beta chain / : / Granulocyte-macrophage colony-stimulating factor / GM-CSF/IL-3/IL-5 receptor common beta subunit, N-terminal / Granulocyte-macrophage colony-stimulating factor signature. / Granulocyte-macrophage colony-simulating factor (GM-CSF) / 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
Granulocyte-macrophage colony-stimulating factor / Granulocyte-macrophage colony-stimulating factor 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_41368.png

Downloads & links

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Map

FileDownload / File: emd_41368.map.gz / Format: CCP4 / Size: 27 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.)
1.24 Å/pix.
x 192 pix.
= 237.389 Å		1.24 Å/pix.
x 192 pix.
= 237.389 Å		1.24 Å/pix.
x 192 pix.
= 237.389 Å

Surface

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Images are generated by Spider.

Voxel sizeX=Y=Z: 1.2364 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.155
Minimum - Maximum-0.061693564 - 1.596538
Average (Standard dev.)0.0007781414 (±0.02086297)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions192192192
Spacing192192192
CellA=B=C: 237.3888 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_41368_msk_1.map
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Half map: #2

Fileemd_41368_half_map_1.map
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Half map: #1

Fileemd_41368_half_map_2.map
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Sample components

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Entire : GM-CSF Receptor Complex

EntireName: GM-CSF Receptor Complex
Components
  • Complex: GM-CSF Receptor Complex
    • Protein or peptide: Granulocyte-macrophage colony-stimulating factor receptor subunit alpha
    • Protein or peptide: Cytokine receptor common subunit beta
    • Protein or peptide: Granulocyte-macrophage colony-stimulating factor

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Supramolecule #1: GM-CSF Receptor Complex

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

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Macromolecule #1: Granulocyte-macrophage colony-stimulating factor receptor subunit...

MacromoleculeName: Granulocyte-macrophage colony-stimulating factor receptor subunit alpha
type: protein_or_peptide / ID: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: DYKDDDDKLI PEKSDLRTVA PASSLNVRFD SRTMNLSWDC QENTTFSKCF LTDKKNRVVE PRLSNNECSC TFREICLHEG VTFEVHVNTS QRGFQQKLLY PNSGREGTAA QNFSCFIYNA DLMNCTWARG PTAPRDVQYF LYIRNSKRRR EIRCPYYIQD SGTHVGCHLD ...String:
DYKDDDDKLI PEKSDLRTVA PASSLNVRFD SRTMNLSWDC QENTTFSKCF LTDKKNRVVE PRLSNNECSC TFREICLHEG VTFEVHVNTS QRGFQQKLLY PNSGREGTAA QNFSCFIYNA DLMNCTWARG PTAPRDVQYF LYIRNSKRRR EIRCPYYIQD SGTHVGCHLD NLSGLTSRNY FLVNGTSREI GIQFFDSLLD TKKIERFNPP SNVTVRCNTT HCLVRWKQPR TYQKLSYLDF QYQLDVHRKN TQPGTENLLI NVSGDLENRY NFPSSEPRAK HSVKIRAADV RILNWSSWSE AIEFGSDDGN LGGGGGSTTA PSAQLKKKLQ ALKKKNAQLK WKLQALKKKL AQGAAEDQVD PRLIDGKHHH HHHHH

UniProtKB: Granulocyte-macrophage colony-stimulating factor receptor subunit alpha

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Macromolecule #2: Cytokine receptor common subunit beta

MacromoleculeName: Cytokine receptor common subunit beta / type: protein_or_peptide / ID: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Recombinant expressionOrganism: Homo sapiens (human)
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: Granulocyte-macrophage colony-stimulating factor

MacromoleculeName: Granulocyte-macrophage colony-stimulating factor / type: protein_or_peptide / ID: 3 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
SequenceString:
DYKDDDDKPA RSPSPSTQPW EHVNAIQEAR RLLNLSRDTA AEMNETVEVI SEMFDLQEPT CLQTRLELYK QGLRGSLTKL KGPLTMMASH YKQHCPPTPE TSCATQIITF ESFKENLKDF LLVIPFDCWE PVQEGAAEDQ VDPRLIDGKH HHHHHHH

UniProtKB: Granulocyte-macrophage colony-stimulating factor

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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: 388885
Initial angle assignmentType: OTHER
Final angle assignmentType: OTHER
FSC plot (resolution estimation)

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