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- PDB-9kmc: Cryo-EM structure of the heterotrimeric interleukin-2 receptor in... -

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Basic information

Entry
Database: PDB / ID: 9kmc
TitleCryo-EM structure of the heterotrimeric interleukin-2 receptor in complex with interleukin-2 and anti-CD25 Fab S417
Components
  • (Interleukin-2 receptor subunit ...) x 2
  • Cytokine receptor common subunit gamma
  • Fab S417 heavy chain
  • Fab S417 light chain
  • Interleukin-2
KeywordsIMMUNE SYSTEM / CYTOKINE
Function / homology
Function and homology information


regulation of T cell tolerance induction / interleukin-2 receptor complex / interleukin-2 receptor activity / mature B cell differentiation / interleukin-15 receptor activity / interleukin-2 binding / CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation / kappa-type opioid receptor binding / response to tacrolimus / regulation of T cell homeostatic proliferation ...regulation of T cell tolerance induction / interleukin-2 receptor complex / interleukin-2 receptor activity / mature B cell differentiation / interleukin-15 receptor activity / interleukin-2 binding / CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation / kappa-type opioid receptor binding / response to tacrolimus / regulation of T cell homeostatic proliferation / regulation of CD4-positive, alpha-beta T cell proliferation / interleukin-2 receptor binding / glycosphingolipid binding / positive regulation of plasma cell differentiation / negative regulation of lymphocyte proliferation / positive regulation of tissue remodeling / activation-induced cell death of T cells / negative regulation of T-helper 17 cell differentiation / positive regulation of T cell differentiation in thymus / lymphocyte differentiation / RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs) / Interleukin-9 signaling / Interleukin-21 signaling / interleukin-7-mediated signaling pathway / leukocyte activation involved in immune response / interleukin-9-mediated signaling pathway / interleukin-4-mediated signaling pathway / positive regulation of isotype switching to IgG isotypes / positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation / interleukin-2-mediated signaling pathway / interleukin-15-mediated signaling pathway / activated T cell proliferation / inflammatory response to antigenic stimulus / cellular homeostasis / STAT3 nuclear events downstream of ALK signaling / Interleukin-15 signaling / cytokine receptor activity / cell surface receptor signaling pathway via STAT / Interleukin-2 signaling / kinase activator activity / natural killer cell activation / positive regulation of regulatory T cell differentiation / negative regulation of B cell apoptotic process / positive regulation of B cell differentiation / positive regulation of immunoglobulin production / positive regulation of T cell differentiation / cytokine binding / positive regulation of dendritic spine development / positive regulation of interleukin-17 production / positive regulation of activated T cell proliferation / immunoglobulin mediated immune response / T cell differentiation / Interleukin receptor SHC signaling / coreceptor activity / negative regulation of T cell proliferation / Notch signaling pathway / positive regulation of B cell proliferation / extrinsic apoptotic signaling pathway in absence of ligand / Interleukin-7 signaling / positive regulation of phagocytosis / cytokine activity / growth factor activity / negative regulation of inflammatory response / positive regulation of type II interferon production / cytokine-mediated signaling pathway / positive regulation of inflammatory response / cell-cell signaling / T cell differentiation in thymus / positive regulation of cytosolic calcium ion concentration / carbohydrate binding / RAF/MAP kinase cascade / positive regulation of cell growth / protein-containing complex assembly / response to ethanol / Interleukin-4 and Interleukin-13 signaling / phospholipase C-activating G protein-coupled receptor signaling pathway / gene expression / adaptive immune response / transcription by RNA polymerase II / cell surface receptor signaling pathway / receptor complex / cell adhesion / endosome / immune response / inflammatory response / external side of plasma membrane / positive regulation of cell population proliferation / apoptotic process / negative regulation of apoptotic process / cell surface / signal transduction / positive regulation of transcription by RNA polymerase II / extracellular space / extracellular region / nucleoplasm / membrane / plasma membrane / cytosol
Similarity search - Function
Interleukin-2 receptor subunit beta, N-terminal / Interleukin-2 receptor subunit beta N-terminal domain 1 / Interleukin-2 receptor alpha / : / : / Cytokine receptor-like factor 2-like, D2 domain / Cytokine receptor-like factor 2, domain 1 / Interleukin-2 / Interleukin-2, conserved site / Interleukin 2 ...Interleukin-2 receptor subunit beta, N-terminal / Interleukin-2 receptor subunit beta N-terminal domain 1 / Interleukin-2 receptor alpha / : / : / Cytokine receptor-like factor 2-like, D2 domain / Cytokine receptor-like factor 2, domain 1 / Interleukin-2 / Interleukin-2, conserved site / Interleukin 2 / Interleukin-2 signature. / Interleukin-2 family / Short hematopoietin receptor family 1 signature. / Short hematopoietin receptor, family 1, conserved site / Sushi repeat (SCR repeat) / Domain abundant in complement control proteins; SUSHI repeat; short complement-like repeat (SCR) / Four-helical cytokine-like, core / Sushi/SCR/CCP domain / Sushi/CCP/SCR domain profile. / Sushi/SCR/CCP superfamily / Fibronectin type 3 domain / Fibronectin type-III domain profile. / Fibronectin type III / Fibronectin type III superfamily / Immunoglobulin-like fold
Similarity search - Domain/homology
Interleukin-2 receptor subunit alpha / Interleukin-2 receptor subunit beta / Cytokine receptor common subunit gamma / Interleukin-2
Similarity search - Component
Biological speciesHomo sapiens (human)
synthetic construct (others)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.97 Å
AuthorsKatsura, K. / Matsumoto, T. / Shirouzu, M.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: To Be Published
Title: CXCR4 induces memory formation over exhaustion in CAR-T cells to achieve durable leukemia targeting
Authors: Itoh-Nakadai, A. / Liang, M. / Ishikawa, F.
History
DepositionNov 15, 2024Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Nov 19, 2025Provider: repository / Type: Initial release
Revision 1.0Nov 19, 2025Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0Nov 19, 2025Data content type: FSC / Data content type: FSC / Provider: repository / Type: Initial release
Revision 1.0Nov 19, 2025Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Nov 19, 2025Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Nov 19, 2025Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Nov 19, 2025Data content type: Mask / Part number: 1 / Data content type: Mask / Provider: repository / Type: Initial release
Revision 1.0Nov 19, 2025Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
A: Interleukin-2 receptor subunit alpha
B: Interleukin-2 receptor subunit beta
C: Cytokine receptor common subunit gamma
D: Interleukin-2
E: Fab S417 heavy chain
F: Fab S417 light chain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)146,77612
Polymers143,9786
Non-polymers2,7986
Water00
1


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

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Components

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Interleukin-2 receptor subunit ... , 2 types, 2 molecules AB

#1: Protein Interleukin-2 receptor subunit alpha / IL-2 receptor subunit alpha / IL-2-RA / IL-2R subunit alpha / IL2-RA / TAC antigen / p55


Mass: 26625.502 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: IL2RA / Production host: Homo sapiens (human) / References: UniProt: P01589
#2: Protein Interleukin-2 receptor subunit beta / IL-2 receptor subunit beta / IL-2R subunit beta / IL-2RB / High affinity IL-2 receptor subunit beta ...IL-2 receptor subunit beta / IL-2R subunit beta / IL-2RB / High affinity IL-2 receptor subunit beta / Interleukin-15 receptor subunit beta / p70-75 / p75


Mass: 25824.219 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: IL2RB, IL15RB / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P14784

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Protein , 2 types, 2 molecules CD

#3: Protein Cytokine receptor common subunit gamma / Interleukin-2 receptor subunit gamma / IL-2 receptor subunit gamma / IL-2R subunit gamma / IL-2RG / ...Interleukin-2 receptor subunit gamma / IL-2 receptor subunit gamma / IL-2R subunit gamma / IL-2RG / gammaC / p64


Mass: 28628.816 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: IL2RG / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P31785
#4: Protein Interleukin-2 / IL-2 / T-cell growth factor / TCGF


Mass: 15435.979 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: IL2 / Production host: Escherichia coli (E. coli) / References: UniProt: P60568

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Antibody , 2 types, 2 molecules EF

#5: Antibody Fab S417 heavy chain


Mass: 24459.379 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) synthetic construct (others) / Production host: Homo sapiens (human)
#6: Antibody Fab S417 light chain


Mass: 23004.434 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) synthetic construct (others) / Production host: Homo sapiens (human)

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Sugars , 4 types, 6 molecules

#7: Polysaccharide 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta- ...2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 570.542 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DGlcpNAcb1-4[LFucpa1-6]DGlcpNAcb1-ROHGlycam Condensed SequenceGMML 1.0
WURCS=2.0/2,3,2/[a2122h-1b_1-5_2*NCC/3=O][a1221m-1a_1-5]/1-1-2/a4-b1_a6-c1WURCSPDB2Glycan 1.1.0
[][D-1-deoxy-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{}[(6+1)][a-L-Fucp]{}}LINUCSPDB-CARE
#8: Polysaccharide beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 586.542 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DManpb1-4DGlcpNAcb1-4DGlcpNAcb1-ROHGlycam Condensed SequenceGMML 1.0
WURCS=2.0/2,3,2/[a2122h-1b_1-5_2*NCC/3=O][a1122h-1b_1-5]/1-1-2/a4-b1_b4-c1WURCSPDB2Glycan 1.1.0
[][D-1-deoxy-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{[(4+1)][b-D-Manp]{}}}LINUCSPDB-CARE
#9: 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.: 2
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
#10: 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.: 1
Source method: isolated from a genetically manipulated source
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

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Details

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

Component
IDNameTypeEntity IDParent-IDSource
1Heterotrimeric interleukin-2 receptor in complex with interleukin-2 and Fab S417COMPLEX#1-#60MULTIPLE SOURCES
2Interleukin-2 receptor subunit alphaCOMPLEX#11RECOMBINANT
3Interleukin-2 receptor subunit betaCOMPLEX#21RECOMBINANT
4Cytokine receptor common subunit gammaCOMPLEX#31RECOMBINANT
5Interleukin-2COMPLEX#41RECOMBINANT
6Fab S417COMPLEX#5-#61RECOMBINANT
Source (natural)
IDEntity assembly-IDOrganismNcbi tax-ID
12Homo sapiens (human)9606
23Homo sapiens (human)9606
34Homo sapiens (human)9606
45Homo sapiens (human)9606
56sythetic construct (others)32600
Source (recombinant)
IDEntity assembly-IDOrganismNcbi tax-ID
12Homo sapiens (human)9606
23Trichoplusia ni (cabbage looper)7111
34Trichoplusia ni (cabbage looper)7111
45Escherichia coli (E. coli)562
56Homo sapiens (human)9606
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: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 800 nm
Image recordingElectron dose: 50.4 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

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Processing

EM softwareName: PHENIX / Version: 1.21.2_5419: / Category: model refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 2.97 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 353002 / Symmetry type: POINT
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.0049170
ELECTRON MICROSCOPYf_angle_d0.54112478
ELECTRON MICROSCOPYf_dihedral_angle_d5.6831473
ELECTRON MICROSCOPYf_chiral_restr0.0641411
ELECTRON MICROSCOPYf_plane_restr0.0041576

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