- EMDB-22098: Interleukin-10 signaling complex with IL-10RA and IL-10RB -
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Basic information
Entry
Database: EMDB / ID: EMD-22098
Title
Interleukin-10 signaling complex with IL-10RA and IL-10RB
Map data
Sharpened map of the hexameric Interleukin-10 signaling complex with IL-10RA and IL-10RB
Sample
Complex: Interleukin-10 signaling complex with IL-10RA and IL-10RB
Complex: Interleukin-10, IL-10RA
Protein or peptide: Interleukin-10
Protein or peptide: Interleukin-10 receptor subunit alpha
Complex: IL-10RB
Protein or peptide: Interleukin-10 receptor subunit beta
Function / homology
Function and homology information
interferon receptor activity / interleukin-10 binding / negative regulation of chronic inflammatory response to antigenic stimulus / interleukin-10 receptor activity / interleukin-10 receptor binding / regulation of response to wounding / interleukin-28 receptor complex / negative regulation of cytokine activity / negative regulation of interleukin-18 production / negative regulation of myeloid dendritic cell activation ...interferon receptor activity / interleukin-10 binding / negative regulation of chronic inflammatory response to antigenic stimulus / interleukin-10 receptor activity / interleukin-10 receptor binding / regulation of response to wounding / interleukin-28 receptor complex / negative regulation of cytokine activity / negative regulation of interleukin-18 production / negative regulation of myeloid dendritic cell activation / negative regulation of interferon-alpha production / negative regulation of chemokine (C-C motif) ligand 5 production / response to carbon monoxide / positive regulation of plasma cell differentiation / positive regulation of B cell apoptotic process / ubiquitin-dependent endocytosis / positive regulation of cellular respiration / chronic inflammatory response to antigenic stimulus / response to inactivity / cytoplasmic sequestering of NF-kappaB / intestinal epithelial structure maintenance / negative regulation of membrane protein ectodomain proteolysis / regulation of isotype switching / negative regulation of heterotypic cell-cell adhesion / negative regulation of cytokine production involved in immune response / type III interferon-mediated signaling pathway / negative regulation of interleukin-1 production / negative regulation of MHC class II biosynthetic process / branching involved in labyrinthine layer morphogenesis / negative regulation of interleukin-8 production / negative regulation of nitric oxide biosynthetic process / negative regulation of interleukin-12 production / type 2 immune response / negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway / endothelial cell apoptotic process / positive regulation of MHC class II biosynthetic process / positive regulation of macrophage activation / leukocyte chemotaxis / positive regulation of heterotypic cell-cell adhesion / positive regulation of signaling receptor activity / CD163 mediating an anti-inflammatory response / negative regulation of cytokine production / positive regulation of immunoglobulin production / Other interleukin signaling / cellular response to hepatocyte growth factor stimulus / Interleukin-20 family signaling / regulation of synapse organization / positive regulation of sprouting angiogenesis / B cell proliferation / negative regulation of B cell proliferation / defense response to protozoan / negative regulation of vascular associated smooth muscle cell proliferation / Interleukin-10 signaling / negative regulation of interleukin-6 production / hemopoiesis / negative regulation of type II interferon production / negative regulation of tumor necrosis factor production / negative regulation of mitotic cell cycle / Nuclear events stimulated by ALK signaling in cancer / positive regulation of cell cycle / negative regulation of T cell proliferation / response to glucocorticoid / positive regulation of vascular associated smooth muscle cell proliferation / positive regulation of endothelial cell proliferation / Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation / negative regulation of autophagy / B cell differentiation / FCGR3A-mediated IL10 synthesis / response to activity / positive regulation of cytokine production / cytokine activity / cellular response to estradiol stimulus / liver regeneration / positive regulation of receptor signaling pathway via JAK-STAT / growth factor activity / response to insulin / response to molecule of bacterial origin / cellular response to virus / cytokine-mediated signaling pathway / positive regulation of DNA-binding transcription factor activity / positive regulation of miRNA transcription / negative regulation of inflammatory response / Signaling by ALK fusions and activated point mutants / signaling receptor activity / regulation of gene expression / cellular response to lipopolysaccharide / Interleukin-4 and Interleukin-13 signaling / defense response to virus / response to lipopolysaccharide / protein dimerization activity / defense response to bacterium / response to xenobiotic stimulus / inflammatory response / immune response / apical plasma membrane / negative regulation of cell population proliferation / negative regulation of apoptotic process / positive regulation of DNA-templated transcription / signal transduction / positive regulation of transcription by RNA polymerase II Similarity search - Function
Interleukin-10 / Interleukin-10 family / Interleukin-10/19/20/22/24/26 family / Interleukin 10 / Interleukin-10, conserved site / Interleukin-10 family signature. / Interferon/interleukin receptor domain / Interferon-alpha/beta receptor, fibronectin type III / Tissue factor / Four-helical cytokine-like, core ...Interleukin-10 / Interleukin-10 family / Interleukin-10/19/20/22/24/26 family / Interleukin 10 / Interleukin-10, conserved site / Interleukin-10 family signature. / Interferon/interleukin receptor domain / Interferon-alpha/beta receptor, fibronectin type III / Tissue factor / Four-helical cytokine-like, core / Fibronectin type-III domain profile. / Fibronectin type III / Fibronectin type III superfamily / Immunoglobulin-like fold Similarity search - Domain/homology
Journal: Science / Year: 2021 Title: Structure-based decoupling of the pro- and anti-inflammatory functions of interleukin-10. Authors: Robert A Saxton / Naotaka Tsutsumi / Leon L Su / Gita C Abhiraman / Kritika Mohan / Lukas T Henneberg / Nanda G Aduri / Cornelius Gati / K Christopher Garcia / Abstract: Interleukin-10 (IL-10) is an immunoregulatory cytokine with both anti-inflammatory and immunostimulatory properties and is frequently dysregulated in disease. We used a structure-based approach to ...Interleukin-10 (IL-10) is an immunoregulatory cytokine with both anti-inflammatory and immunostimulatory properties and is frequently dysregulated in disease. We used a structure-based approach to deconvolute IL-10 pleiotropy by determining the structure of the IL-10 receptor (IL-10R) complex by cryo-electron microscopy at a resolution of 3.5 angstroms. The hexameric structure shows how IL-10 and IL-10Rα form a composite surface to engage the shared signaling receptor IL-10Rβ, enabling the design of partial agonists. IL-10 variants with a range of IL-10Rβ binding strengths uncovered substantial differences in response thresholds across immune cell populations, providing a means of manipulating IL-10 cell type selectivity. Some variants displayed myeloid-biased activity by suppressing macrophage activation without stimulating inflammatory CD8 T cells, thereby uncoupling the major opposing functions of IL-10. These results provide a mechanistic blueprint for tuning the pleiotropic actions of IL-10.
History
Deposition
Jun 2, 2020
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Header (metadata) release
Mar 17, 2021
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Map release
Mar 17, 2021
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Update
Mar 31, 2021
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Current status
Mar 31, 2021
Processing site: RCSB / Status: Released
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Structure visualization
Movie
Surface view with section colored by density value
EMPIAR-10557 (Title: Interleukin-10 signaling complex with IL-10RA and IL-10RB Data size: 5.4 TB Data #1: Unaligned dark-subtracted TIFF movies with a gain reference for the 3D reconstruction of EMD-22098. [micrographs - multiframe])
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