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- EMDB-52665: Cryo-EM structure of human IL-36gamma in complex with the IL-36R ... -

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Basic information

Entry
Database: EMDB / ID: EMD-52665
TitleCryo-EM structure of human IL-36gamma in complex with the IL-36R and IL-1RAcP ectodomains
Map dataCryo-EM map of the extracellular IL-36gamma signaling complex
Sample
  • Complex: Ternary complex of IL-36gamma with the IL-36R and IL-1RAcP ectodomains
    • Protein or peptide: Interleukin-1 receptor accessory protein
    • Protein or peptide: Interleukin-36 gamma
    • Protein or peptide: Interleukin-1 receptor-like 2
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
Keywordscytokine / receptor complex / inflammation / IL-1 family / IMMUNE SYSTEM
Function / homology
Function and homology information


interleukin-33 receptor activity / interleukin-1, type I, activating receptor activity / Interleukin-33 signaling / Interleukin-36 pathway / interleukin-1 receptor activity / negative regulation of interleukin-1 alpha production / trans-synaptic signaling by trans-synaptic complex / Interleukin-38 signaling / microglial cell activation involved in immune response / Receptor-type tyrosine-protein phosphatases ...interleukin-33 receptor activity / interleukin-1, type I, activating receptor activity / Interleukin-33 signaling / Interleukin-36 pathway / interleukin-1 receptor activity / negative regulation of interleukin-1 alpha production / trans-synaptic signaling by trans-synaptic complex / Interleukin-38 signaling / microglial cell activation involved in immune response / Receptor-type tyrosine-protein phosphatases / negative regulation of interleukin-1-mediated signaling pathway / synaptic membrane adhesion / interleukin-33-mediated signaling pathway / regulation of postsynaptic density assembly / positive regulation of interleukin-5 production / positive regulation of interleukin-13 production / ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase / NAD+ nucleosidase activity, cyclic ADP-ribose generating / positive regulation of synapse assembly / interleukin-1 receptor binding / interleukin-1-mediated signaling pathway / positive regulation of cytokine production involved in inflammatory response / negative regulation of interleukin-1 beta production / positive regulation of interleukin-4 production / monocyte differentiation / regulation of presynapse assembly / cellular defense response / coreceptor activity / cytokine activity / negative regulation of inflammatory response / positive regulation of interleukin-6 production / cytokine-mediated signaling pathway / positive regulation of inflammatory response / Interleukin-1 signaling / PIP3 activates AKT signaling / cell-cell signaling / cellular response to lipopolysaccharide / regulation of inflammatory response / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / protein-containing complex assembly / positive regulation of MAPK cascade / positive regulation of canonical NF-kappaB signal transduction / cell surface receptor signaling pathway / immune response / inflammatory response / innate immune response / glutamatergic synapse / cell surface / signal transduction / : / extracellular region / membrane / plasma membrane / cytosol
Similarity search - Function
Interleukin-1 receptor type 1 / Interleukin-1 receptor antagonist/Interleukin-36 / Interleukin-1 receptor type I/II / IL-1Ra-like, immunoglobulin domain / Immunoglobulin domain / Interleukin-1 receptor family / Interleukin-1 homologues / Interleukin-1 family / Interleukin-1 / 18 / Cytokine IL1/FGF ...Interleukin-1 receptor type 1 / Interleukin-1 receptor antagonist/Interleukin-36 / Interleukin-1 receptor type I/II / IL-1Ra-like, immunoglobulin domain / Immunoglobulin domain / Interleukin-1 receptor family / Interleukin-1 homologues / Interleukin-1 family / Interleukin-1 / 18 / Cytokine IL1/FGF / TIR domain / Immunoglobulin domain / Toll - interleukin 1 - resistance / TIR domain profile. / Toll/interleukin-1 receptor homology (TIR) domain / Toll/interleukin-1 receptor homology (TIR) domain superfamily / Immunoglobulin subtype / Immunoglobulin / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / Immunoglobulin-like fold
Similarity search - Domain/homology
Interleukin-1 receptor-like 2 / Interleukin-1 receptor accessory protein / Interleukin-36 gamma
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.27 Å
AuthorsAndries J / Felix J / Clancy DM / Savvides SN
Funding support Belgium, 1 items
OrganizationGrant numberCountry
Research Foundation - Flanders (FWO)1S83421N Belgium
CitationJournal: To Be Published
Title: Structural basis of pro-inflammatory signaling via the IL-36 receptor mediated by IL-36g and IL-37
Authors: Andries J / Toul M / Felix J / Clancy DM / Savvides SN
History
DepositionFeb 3, 2025-
Header (metadata) releaseAug 19, 2026-
Map releaseAug 19, 2026-
UpdateAug 19, 2026-
Current statusAug 19, 2026Processing site: PDBe / Status: Released

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Structure visualization

Supplemental images

emd_52665.png

Downloads & links

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Map

FileDownload / File: emd_52665.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationCryo-EM map of the extracellular IL-36gamma signaling complex
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.74 Å/pix.
x 360 pix.
= 266.4 Å		0.74 Å/pix.
x 360 pix.
= 266.4 Å		0.74 Å/pix.
x 360 pix.
= 266.4 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.74 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.088
Minimum - Maximum-0.36469877 - 0.60783815
Average (Standard dev.)0.00022879374 (±0.010481493)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions360360360
Spacing360360360
CellA=B=C: 266.4 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: Cryo-EM half map of the extracellular IL-36gamma signaling complex

Fileemd_52665_half_map_1.map
AnnotationCryo-EM half map of the extracellular IL-36gamma signaling complex
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: Cryo-EM half map of the extracellular IL-36gamma signaling complex

Fileemd_52665_half_map_2.map
AnnotationCryo-EM half map of the extracellular IL-36gamma signaling complex
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : Ternary complex of IL-36gamma with the IL-36R and IL-1RAcP ectodomains

EntireName: Ternary complex of IL-36gamma with the IL-36R and IL-1RAcP ectodomains
Components
  • Complex: Ternary complex of IL-36gamma with the IL-36R and IL-1RAcP ectodomains
    • Protein or peptide: Interleukin-1 receptor accessory protein
    • Protein or peptide: Interleukin-36 gamma
    • Protein or peptide: Interleukin-1 receptor-like 2
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

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Supramolecule #1: Ternary complex of IL-36gamma with the IL-36R and IL-1RAcP ectodomains

SupramoleculeName: Ternary complex of IL-36gamma with the IL-36R and IL-1RAcP ectodomains
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 92.7 KDa

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Macromolecule #1: Interleukin-1 receptor accessory protein

MacromoleculeName: Interleukin-1 receptor accessory protein / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO / EC number: ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 40.339891 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: SERCDDWGLD TMRQIQVFED EPARIKCPLF EHFLKFNYST AHSAGLTLIW YWTRQDRDLE EPINFRLPEN RISKEKDVLW FRPTLLNDT GNYTCMLRNT TYCSKVAFPL EVVQKDSCFN SPMKLPVHKL YIEYGIQRIT CPNVDGYFPS SVKPTITWYM G CYKIQNFN ...String:
SERCDDWGLD TMRQIQVFED EPARIKCPLF EHFLKFNYST AHSAGLTLIW YWTRQDRDLE EPINFRLPEN RISKEKDVLW FRPTLLNDT GNYTCMLRNT TYCSKVAFPL EVVQKDSCFN SPMKLPVHKL YIEYGIQRIT CPNVDGYFPS SVKPTITWYM G CYKIQNFN NVIPEGMNLS FLIALISNNG NYTCVVTYPE NGRTFHLTRT LTVKVVGSPK NAVPPVIHSP NDHVVYEKEP GE ELLIPCT VYFSFLMDSR NEVWWTIDGK KPDDITIDVT INESISHSRT EDETRTQILS IKKVTSEDLK RSYVCHARSA KGE VAKAAK VKQKVPAPRY TVELACGFGA TDEVD

UniProtKB: Interleukin-1 receptor accessory protein

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Macromolecule #2: Interleukin-36 gamma

MacromoleculeName: Interleukin-36 gamma / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 17.045418 KDa
Recombinant expressionOrganism: Escherichia coli BL21(DE3) (bacteria)
SequenceString:
SMCKPITGTI NDLNQQVWTL QGQNLVAVPR SDSVTPVTVA VITCKYPEAL EQGRGDPIYL GIQNPEMCLY CEKVGEQPTL QLKEQKIMD LYGQPEPVKP FLFYRAKTGR TSTLESVAFP DWFIASSKRD QPIILTSELG KSYNTAFELN IND

UniProtKB: Interleukin-36 gamma

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Macromolecule #3: Interleukin-1 receptor-like 2

MacromoleculeName: Interleukin-1 receptor-like 2 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO / EC number: ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 36.407152 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: DGCKDIFMKN EILSASQPFA FNCTFPPITS GEVSVTWYKN SSKIPVSKII QSRIHQDETW ILFLPMEWGD SGVYQCVIKG RDSCHRIHV NLTVFEKHWC DTSIGGLPNL SDEYKQILHL GKDDSLTCHL HFPKSSVLGP IKWYKDCNEI KGERFTVLET R LLVSNVSA ...String:
DGCKDIFMKN EILSASQPFA FNCTFPPITS GEVSVTWYKN SSKIPVSKII QSRIHQDETW ILFLPMEWGD SGVYQCVIKG RDSCHRIHV NLTVFEKHWC DTSIGGLPNL SDEYKQILHL GKDDSLTCHL HFPKSSVLGP IKWYKDCNEI KGERFTVLET R LLVSNVSA EDRGNYACQA ILTHSGKQYE VLNGITVSIT ERAGYGGSVP KIIYPKNHSI EVQLGTTLIV DCNVTDTKDN TN LRSWRVN NTLVDDYYDE SKRIREGVET HVSFREHNLY TVNITFLEVK MEDYGLPFMC HAGVSTAYII LQLPAPDFRD EVD

UniProtKB: Interleukin-1 receptor-like 2

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Macromolecule #5: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 5 / Number of copies: 9 / 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

Concentration3.3 mg/mL
BufferpH: 7.4
Component:
ConcentrationFormulaName
20.0 mMHEPES4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid
150.0 mMNaClsodium chloride
0.1 mMDDMdodecyl maltoside

Details: DDM was added before application on grids
GridModel: Quantifoil R2/1 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE
VitrificationCryogen name: ETHANE / Chamber humidity: 95 % / Chamber temperature: 295.15 K / Instrument: LEICA EM GP

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Electron microscopy

MicroscopeJEOL CRYO ARM 300
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Number grids imaged: 1 / Number real images: 8828 / Average exposure time: 3.37 sec. / Average electron dose: 61.8 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.7 µm / Nominal defocus min: 0.8 µm
Sample stageCooling holder cryogen: NITROGEN

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Image processing

Particle selectionNumber selected: 771846
CTF correctionSoftware - Name: cryoSPARC (ver. 4.2.1) / Type: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.27 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 4.2.1) / Number images used: 201760
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 4.2.1)
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 4.2.1)
Final 3D classificationNumber classes: 5 / Software - Name: cryoSPARC (ver. 4.2.1)
FSC plot (resolution estimation)

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Atomic model buiding 1

Initial modelChain - Source name: AlphaFold / Chain - Initial model type: in silico model
DetailsNAMDINATOR was used for flexible fitting of the AlphaFold model in the final cryo-EM map
RefinementProtocol: FLEXIBLE FIT
Output model

PDB-9i7x:
Cryo-EM structure of human IL-36gamma in complex with the IL-36R and IL-1RAcP ectodomains

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