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- EMDB-26835: Structure of the IL-25-IL-17RB-IL-17RA ternary complex -

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Basic information

Entry
Database: EMDB / ID: EMD-26835
TitleStructure of the IL-25-IL-17RB-IL-17RA ternary complex
Map dataFull map
Sample
  • Complex: ternary IL-25-IL-17RB-IL-17RA complex
    • Protein or peptide: Interleukin-25
    • Protein or peptide: Interleukin-17 receptor B
    • Protein or peptide: Interleukin-17 receptor A
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
KeywordsReceptor complex / IL-17E / IL-25 / IL-17RB / IL-17RA / cytokine
Function / homology
Function and homology information


interleukin-17E receptor binding / interleukin-17 receptor activity / eosinophil differentiation / granulocyte chemotaxis / Interleukin-17 signaling / T-helper 17 type immune response / interleukin-17A-mediated signaling pathway / positive regulation of interleukin-23 production / positive regulation of chemokine (C-X-C motif) ligand 1 production / response to nematode ...interleukin-17E receptor binding / interleukin-17 receptor activity / eosinophil differentiation / granulocyte chemotaxis / Interleukin-17 signaling / T-helper 17 type immune response / interleukin-17A-mediated signaling pathway / positive regulation of interleukin-23 production / positive regulation of chemokine (C-X-C motif) ligand 1 production / response to nematode / response to fungus / interleukin-17-mediated signaling pathway / positive regulation of interleukin-13 production / positive regulation of interleukin-5 production / fibroblast activation / positive regulation of cytokine production involved in inflammatory response / inflammatory response to antigenic stimulus / cytokine receptor activity / defense response to fungus / cytokine activity / regulation of cell growth / response to virus / protein catabolic process / defense response / positive regulation of interleukin-6 production / positive regulation of inflammatory response / cell surface receptor signaling pathway / inflammatory response / intracellular membrane-bounded organelle / signaling receptor binding / innate immune response / SARS-CoV-2 activates/modulates innate and adaptive immune responses / positive regulation of transcription by RNA polymerase II / extracellular space / extracellular region / membrane / plasma membrane
Similarity search - Function
Interleukin-17 receptor, fibronectin-III-like domain 1 / Interleukin-17 receptor A/B, FnIII-like domain 1 superfamily / Interleukin-17 receptor A/B, FnIII-like domain 2 superfamily / Interleukin-17 receptor, fibronectin-III-like domain 1 / Interleukin 17 receptor D / Interleukin-17 receptor-like / SEFIR domain / SEFIR domain / SEFIR domain profile. / Interleukin-17 family ...Interleukin-17 receptor, fibronectin-III-like domain 1 / Interleukin-17 receptor A/B, FnIII-like domain 1 superfamily / Interleukin-17 receptor A/B, FnIII-like domain 2 superfamily / Interleukin-17 receptor, fibronectin-III-like domain 1 / Interleukin 17 receptor D / Interleukin-17 receptor-like / SEFIR domain / SEFIR domain / SEFIR domain profile. / Interleukin-17 family / Interleukin-17 / Cystine-knot cytokine
Similarity search - Domain/homology
Interleukin-17 receptor A / Interleukin-25 / Interleukin-17 receptor B
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.7 Å
AuthorsWilson SC / Caveney NA / Jude KM / Garcia KC
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)R01-AI51321 United States
CitationJournal: Nature / Year: 2022
Title: Organizing structural principles of the IL-17 ligand-receptor axis.
Authors: Steven C Wilson / Nathanael A Caveney / Michelle Yen / Christoph Pollmann / Xinyu Xiang / Kevin M Jude / Maximillian Hafer / Naotaka Tsutsumi / Jacob Piehler / K Christopher Garcia /
Abstract: The IL-17 family of cytokines and receptors have central roles in host defence against infection and development of inflammatory diseases. The compositions and structures of functional IL-17 family ...The IL-17 family of cytokines and receptors have central roles in host defence against infection and development of inflammatory diseases. The compositions and structures of functional IL-17 family ligand-receptor signalling assemblies remain unclear. IL-17E (also known as IL-25) is a key regulator of type 2 immune responses and driver of inflammatory diseases, such as allergic asthma, and requires both IL-17 receptor A (IL-17RA) and IL-17RB to elicit functional responses. Here we studied IL-25-IL-17RB binary and IL-25-IL-17RB-IL-17RA ternary complexes using a combination of cryo-electron microscopy, single-molecule imaging and cell-based signalling approaches. The IL-25-IL-17RB-IL-17RA ternary signalling assembly is a C2-symmetric complex in which the IL-25-IL-17RB homodimer is flanked by two 'wing-like' IL-17RA co-receptors through a 'tip-to-tip' geometry that is the key receptor-receptor interaction required for initiation of signal transduction. IL-25 interacts solely with IL-17RB to allosterically promote the formation of the IL-17RB-IL-17RA tip-to-tip interface. The resulting large separation between the receptors at the membrane-proximal level may reflect proximity constraints imposed by the intracellular domains for signalling. Cryo-electron microscopy structures of IL-17A-IL-17RA and IL-17A-IL-17RA-IL-17RC complexes reveal that this tip-to-tip architecture is a key organizing principle of the IL-17 receptor family. Furthermore, these studies reveal dual actions for IL-17RA sharing among IL-17 cytokine complexes, by either directly engaging IL-17 cytokines or alternatively functioning as a co-receptor.
History
DepositionMay 3, 2022-
Header (metadata) releaseJul 27, 2022-
Map releaseJul 27, 2022-
UpdateOct 30, 2024-
Current statusOct 30, 2024Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_26835.png

Downloads & links

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Map

FileDownload / File: emd_26835.map.gz / Format: CCP4 / Size: 216 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationFull map
Projections & slices

Image control

Size
Brightness
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Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.85 Å/pix.
x 384 pix.
= 327.206 Å		0.85 Å/pix.
x 384 pix.
= 327.206 Å		0.85 Å/pix.
x 384 pix.
= 327.206 Å

Surface

Projections

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Images are generated by Spider.

Voxel sizeX=Y=Z: 0.8521 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.036
Minimum - Maximum-0.014682162 - 1.9404339
Average (Standard dev.)0.00070858793 (±0.015882358)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions384384384
Spacing384384384
CellA=B=C: 327.20642 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_26835_msk_1.map
Projections & Slices
AxesZYX

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Histogram

Histogram (log scale)

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Half map: Half map B

Fileemd_26835_half_map_1.map
AnnotationHalf map B
Projections & Slices
AxesZYX

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Histogram

Histogram (log scale)

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Half map: Half map A

Fileemd_26835_half_map_2.map
AnnotationHalf map A
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Sample components

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Entire : ternary IL-25-IL-17RB-IL-17RA complex

EntireName: ternary IL-25-IL-17RB-IL-17RA complex
Components
  • Complex: ternary IL-25-IL-17RB-IL-17RA complex
    • Protein or peptide: Interleukin-25
    • Protein or peptide: Interleukin-17 receptor B
    • Protein or peptide: Interleukin-17 receptor A
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

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Supramolecule #1: ternary IL-25-IL-17RB-IL-17RA complex

SupramoleculeName: ternary IL-25-IL-17RB-IL-17RA complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Interleukin-25

MacromoleculeName: Interleukin-25 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 21.490201 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
DASATHTYSH WPSCCPSKGQ DTSEELLRWS TVPVPPLEPA RPNRHPESCR ASEDGPLNSR AISPWRYELD RDLNRLPQDL YHARCLCPH CVSLQTGSHM DPRGNSELLY HNQTVFYRRP CHGEKGTHKG YCLERRLYRV SLACVCVRPR VMGAPAALEV L FQGPGAAG LNDIFEAQKI EWHEHHHHHH

UniProtKB: Interleukin-25

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Macromolecule #2: Interleukin-17 receptor B

MacromoleculeName: Interleukin-17 receptor B / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 33.649098 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: REPTVQCGSE TGPSPEWMLQ HDLIPGDLRD LRVEPVTTSV ATGDYSILMN VSWVLRADAS IRLLKATKIC VTGKSNFQSY SCVRCNYTE AFQTQTRPSG GKWTFSYIGF PVELNTVYFI GAHNIPNANM NEDGPSMSVN FTSPGCLDHI MKYKKKCVKA G SLWDPNIT ...String:
REPTVQCGSE TGPSPEWMLQ HDLIPGDLRD LRVEPVTTSV ATGDYSILMN VSWVLRADAS IRLLKATKIC VTGKSNFQSY SCVRCNYTE AFQTQTRPSG GKWTFSYIGF PVELNTVYFI GAHNIPNANM NEDGPSMSVN FTSPGCLDHI MKYKKKCVKA G SLWDPNIT ACKKNEETVE VNFTTTPLGN RYMALIQHST IIGFSQVFEP HQKKQTRASV VIPVTGDSEG ATVQLTPYFP TC GSDCIRH KGTVVLCPQT GVPFPLDNNK SKPGAAALEV LFQGPGAAED QVDPRLIDGK HHHHHHHH

UniProtKB: Interleukin-17 receptor B

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Macromolecule #3: Interleukin-17 receptor A

MacromoleculeName: Interleukin-17 receptor A / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 36.888617 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: LRLLDHRALV CSQPGLNCTV KNSTCLDDSW IHPRNLTPSS PKDLQIQLHF AHTQQGDLFP VAHIEWTLQT DASILYLEGA ELSVLQLNT NERLCVRFEF LSKLRHHHRR WRFTFSHFVV DPDQEYEVTV HHLPKPIPDG DPNHQSKNFL VPDCEHARMK V TTPCMSSG ...String:
LRLLDHRALV CSQPGLNCTV KNSTCLDDSW IHPRNLTPSS PKDLQIQLHF AHTQQGDLFP VAHIEWTLQT DASILYLEGA ELSVLQLNT NERLCVRFEF LSKLRHHHRR WRFTFSHFVV DPDQEYEVTV HHLPKPIPDG DPNHQSKNFL VPDCEHARMK V TTPCMSSG SLWDPNITVE TLEAHQLRVS FTLWNESTHY QILLTSFPHM ENHSCFEHMH HIPAPRPEEF HQRSNVTLTL RN LKGCCRH QVQIQPFFSS CLNDCLRHSA TVSCPEMPDT PEPIPDYMSA ALEVLFQGPG AAEDQVDPRL IDGKHHHHHH HH

UniProtKB: Interleukin-17 receptor A

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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: 14 / 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: 7.4
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 53.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: OTHER / Imaging mode: OTHER / Nominal defocus max: 2.2 µm / Nominal defocus min: 0.8 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: INSILICO MODEL
Final reconstructionApplied symmetry - Point group: C2 (2 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 3.7 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 1287497
Initial angle assignmentType: OTHER
Final angle assignmentType: OTHER
FSC plot (resolution estimation)

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