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- EMDB-44791: Structure of the IFN-lambda3/IFN-lambdaR1/IL-10Rbeta receptor com... -
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Open data
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Basic information
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Title | Structure of the IFN-lambda3/IFN-lambdaR1/IL-10Rbeta receptor complex with an engineered IL-10Rbeta | |||||||||
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![]() | INTERFERON / CYTOKINE / CYTOKINE RECEPTOR / TYPE III INTERFERON | |||||||||
Function / homology | ![]() interleukin-10 receptor activity / response to type III interferon / interleukin-28 receptor complex / mucosal immune response / positive regulation of cellular respiration / type III interferon-mediated signaling pathway / interleukin-10-mediated signaling pathway / regulation of defense response to virus by host / cytokine receptor activity / Other interleukin signaling ...interleukin-10 receptor activity / response to type III interferon / interleukin-28 receptor complex / mucosal immune response / positive regulation of cellular respiration / type III interferon-mediated signaling pathway / interleukin-10-mediated signaling pathway / regulation of defense response to virus by host / cytokine receptor activity / Other interleukin signaling / negative regulation of viral genome replication / Interleukin-20 family signaling / Interleukin-10 signaling / cell surface receptor signaling pathway via JAK-STAT / coreceptor activity / cytokine activity / positive regulation of receptor signaling pathway via JAK-STAT / cytokine-mediated signaling pathway / cellular response to virus / positive regulation of immune response / signaling receptor activity / defense response to virus / immune response / inflammatory response / signaling receptor binding / negative regulation of cell population proliferation / innate immune response / signal transduction / extracellular space / extracellular region / membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.0 Å | |||||||||
![]() | Zhang B / Grubbe WS / Mendoza JL / Zhao M | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural studies of the IFNλ4 receptor complex using cryoEM enabled by protein engineering. Authors: William S Grubbe / Bixia Zhang / Aileen Kauffman / Fabian Byléhn / Kasia Padoł / Hae-Gwang Jung / Seung Bum Park / Jessica M Priest / Engin Özkan / Juan J de Pablo / T Jake Liang / ...Authors: William S Grubbe / Bixia Zhang / Aileen Kauffman / Fabian Byléhn / Kasia Padoł / Hae-Gwang Jung / Seung Bum Park / Jessica M Priest / Engin Özkan / Juan J de Pablo / T Jake Liang / Minglei Zhao / Juan L Mendoza / ![]() Abstract: IFNλ4 has posed a conundrum in human immunology since its discovery in 2013, with its expression linked to complications with viral clearance. While genetic and cellular studies revealed the ...IFNλ4 has posed a conundrum in human immunology since its discovery in 2013, with its expression linked to complications with viral clearance. While genetic and cellular studies revealed the detrimental effects of IFNλ4 expression, extensive structural and functional characterization has been limited by the inability to express and purify the protein, complicating explanations of its paradoxical behavior. In this work, we report a method for robust production of IFNλ4. We then use yeast surface display to affinity-mature IL10Rβ and solve the 72 kilodalton structures of IFNλ4 (3.26 Å) and IFNλ3 (3.00 Å) in complex with their receptors IFNλR1 and IL10Rβ using cryogenic electron microscopy. Comparison of the structures highlights differences in receptor engagement and reveals a distinct 12-degree rotation in overall receptor geometry, providing a potential mechanistic explanation for differences in cell signaling, downstream gene induction, and antiviral activities. Further, we perform a structural analysis using molecular modeling and simulation to identify a unique region of IFNλ4 that, when replaced, enables secretion of the protein from cells. These findings provide a structural and functional understanding of the IFNλ4 protein and enable future comprehensive studies towards correcting IFNλ4 dysfunction in large populations of affected patients. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 38 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 16.9 KB 16.9 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 7.9 KB | Display | ![]() |
Images | ![]() | 69 KB | ||
Filedesc metadata | ![]() | 6.4 KB | ||
Others | ![]() ![]() | 31.3 MB 31.4 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 816.8 KB | Display | ![]() |
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Full document | ![]() | 816.4 KB | Display | |
Data in XML | ![]() | 13.5 KB | Display | |
Data in CIF | ![]() | 19.2 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 9bpvMC ![]() 9bpuC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.065 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_44791_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_44791_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
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Sample components
-Entire : Structure of the IFN-lambda3/IFN-lambdaR1/IL-10Rbeta receptor com...
Entire | Name: Structure of the IFN-lambda3/IFN-lambdaR1/IL-10Rbeta receptor complex with an engineered IL-10Rbeta |
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Components |
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-Supramolecule #1: Structure of the IFN-lambda3/IFN-lambdaR1/IL-10Rbeta receptor com...
Supramolecule | Name: Structure of the IFN-lambda3/IFN-lambdaR1/IL-10Rbeta receptor complex with an engineered IL-10Rbeta type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 71.742 KDa |
-Macromolecule #1: Interleukin-10 receptor subunit beta
Macromolecule | Name: Interleukin-10 receptor subunit beta / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 24.773643 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: GSMVPPPENV RMNSVNFKNI LQWESPAFAK GQLTFTAQYL SYRIFQDKCM QTTLTECDFS SLSKYGDHTL RVRAEFADEH SDWVQITFC PVDDTIIGPP GMQVEVLADS LHMRFLAPKI ENEYETWTMK DMYNSWTYNV QYWKQGTDEK FQITPQYDFE V LRNLEPRT ...String: GSMVPPPENV RMNSVNFKNI LQWESPAFAK GQLTFTAQYL SYRIFQDKCM QTTLTECDFS SLSKYGDHTL RVRAEFADEH SDWVQITFC PVDDTIIGPP GMQVEVLADS LHMRFLAPKI ENEYETWTMK DMYNSWTYNV QYWKQGTDEK FQITPQYDFE V LRNLEPRT TYCVQVRGFL PDRNKAGEWS EPVCEQTTHD ETVPSAAAHH HHHH UniProtKB: Interleukin-10 receptor subunit beta |
-Macromolecule #2: Interferon lambda receptor 1
Macromolecule | Name: Interferon lambda receptor 1 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 23.628096 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: RPRLAPPQNV TLLSQNFSVY LTWLPGLGNP QDVTYFVAYQ SSPTRRRWRE VEECAGTKEL LCSMMCLKKQ DLYNKFKGRV RTVSPSSKS PWVESEYLDY LFEVEPAPPV LVLTQTEEIL SANATYQLPP CMPPLDLKYE VAFWKEGAGN KTLFPVTPHG Q PVQITLQP ...String: RPRLAPPQNV TLLSQNFSVY LTWLPGLGNP QDVTYFVAYQ SSPTRRRWRE VEECAGTKEL LCSMMCLKKQ DLYNKFKGRV RTVSPSSKS PWVESEYLDY LFEVEPAPPV LVLTQTEEIL SANATYQLPP CMPPLDLKYE VAFWKEGAGN KTLFPVTPHG Q PVQITLQP AASEHHCLSA RTIYTFSVPK YSKFSKPTCF LLEVPEANAA A UniProtKB: Interferon lambda receptor 1 |
-Macromolecule #3: Interferon lambda-3
Macromolecule | Name: Interferon lambda-3 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 19.877871 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: GSARGCHIAQ FKSLSPQELQ AFKRAKDALE ESLLLKDCKC RSRLFPRTWD LRQLQVRERP VALEAELALT LKVLEATADT DPALGDVLD QPLHTLHHIL SQLRACIQPQ PTAGPRTRGR LHHWLHRLQE APKKESPGCL EASVTFNLFR LLTRDLNCVA S GDLCVAAA HHHHHHHH UniProtKB: Interferon lambda-3 |
-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: 2 / 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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![]() | single particle reconstruction |
Aggregation state | 2D array |
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Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 0.9 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |