+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-26836 | |||||||||
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Title | Structure of the IL-17A-IL-17RA binary complex | |||||||||
Map data | Sharpened map | |||||||||
Sample |
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Function / homology | Function and homology information interleukin-17 receptor activity / positive regulation of interleukin-16 production / granulocyte migration / granulocyte chemotaxis / positive regulation of antimicrobial peptide production / Interleukin-17 signaling / T-helper 17 type immune response / interleukin-17A-mediated signaling pathway / negative regulation of inflammatory response to wounding / intestinal epithelial structure maintenance ...interleukin-17 receptor activity / positive regulation of interleukin-16 production / granulocyte migration / granulocyte chemotaxis / positive regulation of antimicrobial peptide production / Interleukin-17 signaling / T-helper 17 type immune response / interleukin-17A-mediated signaling pathway / negative regulation of inflammatory response to wounding / intestinal epithelial structure maintenance / positive regulation of interleukin-23 production / cell death / positive regulation of chemokine (C-X-C motif) ligand 1 production / interleukin-17-mediated signaling pathway / positive regulation of bicellular tight junction assembly / positive regulation of interleukin-13 production / positive regulation of interleukin-5 production / fibroblast activation / positive regulation of osteoclast differentiation / positive regulation of cytokine production involved in inflammatory response / keratinocyte proliferation / cellular response to interleukin-1 / defense response to fungus / keratinocyte differentiation / Notch signaling pathway / positive regulation of interleukin-12 production / positive regulation of interleukin-1 beta production / cytokine activity / response to virus / protein catabolic process / positive regulation of interleukin-6 production / response to wounding / positive regulation of inflammatory response / positive regulation of tumor necrosis factor production / cell-cell signaling / gene expression / Interleukin-4 and Interleukin-13 signaling / defense response to Gram-negative bacterium / adaptive immune response / cell surface receptor signaling pathway / defense response to Gram-positive bacterium / inflammatory response / immune response / protein heterodimerization activity / external side of plasma membrane / innate immune response / signaling receptor binding / apoptotic process / SARS-CoV-2 activates/modulates innate and adaptive immune responses / protein homodimerization activity / positive regulation of transcription by RNA polymerase II / extracellular space / extracellular region / plasma membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.5 Å | |||||||||
Authors | Wilson SC / Caveney NA / Jude KM / Garcia KC | |||||||||
Funding support | United States, 1 items
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Citation | Journal: 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 |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_26836.map.gz | 54.1 MB | EMDB map data format | |
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Header (meta data) | emd-26836-v30.xml emd-26836.xml | 15.5 KB 15.5 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_26836_fsc.xml | 8.4 KB | Display | FSC data file |
Images | emd_26836.png | 75.3 KB | ||
Masks | emd_26836_msk_1.map | 64 MB | Mask map | |
Others | emd_26836_half_map_1.map.gz emd_26836_half_map_2.map.gz | 59.5 MB 59.5 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-26836 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-26836 | HTTPS FTP |
-Validation report
Summary document | emd_26836_validation.pdf.gz | 534.6 KB | Display | EMDB validaton report |
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Full document | emd_26836_full_validation.pdf.gz | 534.1 KB | Display | |
Data in XML | emd_26836_validation.xml.gz | 15.9 KB | Display | |
Data in CIF | emd_26836_validation.cif.gz | 20.7 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26836 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26836 | HTTPS FTP |
-Related structure data
Related structure data | 7uwmMC 7uwjC 7uwkC 7uwlC 7uwnC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_26836.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | Sharpened map | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.066 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_26836_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: Half map A
File | emd_26836_half_map_1.map | ||||||||||||
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Annotation | Half map A | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map B
File | emd_26836_half_map_2.map | ||||||||||||
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Annotation | Half map B | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : IL-17A-IL-17RA binary complex
Entire | Name: IL-17A-IL-17RA binary complex |
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Components |
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-Supramolecule #1: IL-17A-IL-17RA binary complex
Supramolecule | Name: IL-17A-IL-17RA binary complex / type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Homo sapiens (human) |
-Macromolecule #1: Interleukin-17A
Macromolecule | Name: Interleukin-17A / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 19.254625 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: ITIPRNPGCP NSEDKNFPRT VMVNLNIHNR NTNTNPKRSS DYYNRSTSPW NLHRNEDPER YPSVIWEAKC RHLGCINADG NVDYHMNSV PIQQEILVLR REPPHCPNSF RLEKILVSVG CTCVTPIVHH VAGAPGSALE VLFQGPGAAG LNDIFEAQKI E WHEHHHHH H |
-Macromolecule #2: Interleukin-17 receptor A
Macromolecule | Name: Interleukin-17 receptor A / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 31.585826 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: 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 TVSCP |
-Macromolecule #4: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 4 / Number of copies: 7 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | TFS KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: OTHER / Imaging mode: OTHER / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.8 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |