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- EMDB-26834: Structure of the higher-order IL-25-IL-17RB complex -

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Basic information

Entry
Database: EMDB / ID: EMD-26834
TitleStructure of the higher-order IL-25-IL-17RB complex
Map dataFull map
Sample
  • Complex: higher-order IL-25-IL-17RB complex
    • Protein or peptide: Interleukin-25Interleukin 25
    • Protein or peptide: Interleukin-17 receptor B
Function / homology
Function and homology information


interleukin-17E receptor binding / interleukin-17 receptor activity / eosinophil differentiation / Interleukin-17 signaling / response to nematode / response to fungus / inflammatory response to antigenic stimulus / cytokine receptor activity / cytokine activity / regulation of cell growth ...interleukin-17E receptor binding / interleukin-17 receptor activity / eosinophil differentiation / Interleukin-17 signaling / response to nematode / response to fungus / inflammatory response to antigenic stimulus / cytokine receptor activity / cytokine activity / regulation of cell growth / defense response / intracellular membrane-bounded organelle / positive regulation of transcription by RNA polymerase II / extracellular space / extracellular region / membrane / plasma membrane
Similarity search - Function
Interleukin 17 receptor D / 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-like / SEFIR domain / SEFIR domain / SEFIR domain profile. / Interleukin-17 family ...Interleukin 17 receptor D / 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-like / SEFIR domain / SEFIR domain / SEFIR domain profile. / Interleukin-17 family / Interleukin-17 / Cystine-knot cytokine
Similarity search - Domain/homology
Interleukin-25 / Interleukin-17 receptor B
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 4.4 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-
UpdateSep 28, 2022-
Current statusSep 28, 2022Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_26834.map.gz / Format: CCP4 / Size: 96.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationFull map
Voxel sizeX=Y=Z: 1.704 Å
Density
Contour LevelBy AUTHOR: 0.1
Minimum - Maximum-0.070087165 - 1.4835895
Average (Standard dev.)0.00027079287 (±0.008866211)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions294294294
Spacing294294294
CellA=B=C: 500.976 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_26834_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: Half map A

Fileemd_26834_half_map_1.map
AnnotationHalf map A
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: Half map B

Fileemd_26834_half_map_2.map
AnnotationHalf map B
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Sample components

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Entire : higher-order IL-25-IL-17RB complex

EntireName: higher-order IL-25-IL-17RB complex
Components
  • Complex: higher-order IL-25-IL-17RB complex
    • Protein or peptide: Interleukin-25Interleukin 25
    • Protein or peptide: Interleukin-17 receptor B

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Supramolecule #1: higher-order IL-25-IL-17RB complex

SupramoleculeName: higher-order IL-25-IL-17RB complex / type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)
Recombinant expressionOrganism: Homo sapiens (human)

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Macromolecule #1: Interleukin-25

MacromoleculeName: Interleukin-25 / type: protein_or_peptide / ID: 1 / Number of copies: 6 / 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

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Macromolecule #2: Interleukin-17 receptor B

MacromoleculeName: Interleukin-17 receptor B / type: protein_or_peptide / ID: 2 / Number of copies: 6 / 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

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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
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
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 53.0 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Initial angle assignmentType: OTHER
Final angle assignmentType: OTHER
Final reconstructionResolution.type: BY AUTHOR / Resolution: 4.4 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 297300
FSC plot (resolution estimation)

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