+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-4399 | |||||||||
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Title | Cryo-EM structure of the RIP2 CARD filament | |||||||||
Map data | ||||||||||
Sample |
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Function / homology | Function and homology information response to interleukin-18 / positive regulation of T-helper 1 cell differentiation / toll-like receptor 2 signaling pathway / positive regulation of cytokine-mediated signaling pathway / immature T cell proliferation in thymus / positive regulation of T-helper 1 type immune response / LIM domain binding / positive regulation of xenophagy / CD4-positive, alpha-beta T cell proliferation / xenophagy ...response to interleukin-18 / positive regulation of T-helper 1 cell differentiation / toll-like receptor 2 signaling pathway / positive regulation of cytokine-mediated signaling pathway / immature T cell proliferation in thymus / positive regulation of T-helper 1 type immune response / LIM domain binding / positive regulation of xenophagy / CD4-positive, alpha-beta T cell proliferation / xenophagy / nucleotide-binding oligomerization domain containing 1 signaling pathway / positive regulation of protein K63-linked ubiquitination / cellular response to muramyl dipeptide / caspase binding / positive regulation of immature T cell proliferation in thymus / CARD domain binding / JUN kinase kinase kinase activity / positive regulation of CD4-positive, alpha-beta T cell proliferation / cellular response to peptidoglycan / response to interleukin-12 / activation of cysteine-type endopeptidase activity / nucleotide-binding oligomerization domain containing 2 signaling pathway / positive regulation of macrophage cytokine production / toll-like receptor 4 signaling pathway / response to exogenous dsRNA / positive regulation of interferon-alpha production / cellular response to lipoteichoic acid / canonical NF-kappaB signal transduction / signaling adaptor activity / positive regulation of chemokine production / JNK cascade / lipopolysaccharide-mediated signaling pathway / ERK1 and ERK2 cascade / p75NTR recruits signalling complexes / positive regulation of interleukin-2 production / positive regulation of interferon-beta production / positive regulation of interleukin-12 production / response to interleukin-1 / JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 / positive regulation of peptidyl-threonine phosphorylation / positive regulation of protein ubiquitination / positive regulation of interleukin-1 beta production / activated TAK1 mediates p38 MAPK activation / positive regulation of JNK cascade / non-specific protein-tyrosine kinase / TAK1-dependent IKK and NF-kappa-B activation / NOD1/2 Signaling Pathway / non-membrane spanning protein tyrosine kinase activity / protein homooligomerization / positive regulation of interleukin-6 production / Interleukin-1 signaling / cytokine-mediated signaling pathway / positive regulation of peptidyl-tyrosine phosphorylation / Ovarian tumor domain proteases / positive regulation of type II interferon production / positive regulation of tumor necrosis factor production / Downstream TCR signaling / positive regulation of peptidyl-serine phosphorylation / positive regulation of NF-kappaB transcription factor activity / positive regulation of protein binding / T cell receptor signaling pathway / positive regulation of canonical NF-kappaB signal transduction / vesicle / adaptive immune response / positive regulation of ERK1 and ERK2 cascade / cytoskeleton / non-specific serine/threonine protein kinase / defense response to Gram-positive bacterium / defense response to bacterium / inflammatory response / positive regulation of apoptotic process / phosphorylation / signaling receptor binding / protein serine kinase activity / innate immune response / protein serine/threonine kinase activity / apoptotic process / SARS-CoV-2 activates/modulates innate and adaptive immune responses / endoplasmic reticulum / signal transduction / protein homodimerization activity / positive regulation of transcription by RNA polymerase II / protein-containing complex / ATP binding / identical protein binding / plasma membrane / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | helical reconstruction / cryo EM / Resolution: 3.94 Å | |||||||||
Authors | Pellegrini E / Cusack S / Desfosses A / Schoehn G / Malet H / Gutsche I / Sachse C / Hons M | |||||||||
Citation | Journal: Nat Commun / Year: 2018 Title: RIP2 filament formation is required for NOD2 dependent NF-κB signalling. Authors: Erika Pellegrini / Ambroise Desfosses / Arndt Wallmann / Wiebke Manuela Schulze / Kristina Rehbein / Philippe Mas / Luca Signor / Stephanie Gaudon / Grasilda Zenkeviciute / Michael Hons / ...Authors: Erika Pellegrini / Ambroise Desfosses / Arndt Wallmann / Wiebke Manuela Schulze / Kristina Rehbein / Philippe Mas / Luca Signor / Stephanie Gaudon / Grasilda Zenkeviciute / Michael Hons / Helene Malet / Irina Gutsche / Carsten Sachse / Guy Schoehn / Hartmut Oschkinat / Stephen Cusack / Abstract: Activation of the innate immune pattern recognition receptor NOD2 by the bacterial muramyl-dipeptide peptidoglycan fragment triggers recruitment of the downstream adaptor kinase RIP2, eventually ...Activation of the innate immune pattern recognition receptor NOD2 by the bacterial muramyl-dipeptide peptidoglycan fragment triggers recruitment of the downstream adaptor kinase RIP2, eventually leading to NF-κB activation and proinflammatory cytokine production. Here we show that full-length RIP2 can form long filaments mediated by its caspase recruitment domain (CARD), in common with other innate immune adaptor proteins. We further show that the NOD2 tandem CARDs bind to one end of the RIP2 CARD filament, suggesting a mechanism for polar filament nucleation by activated NOD2. We combine X-ray crystallography, solid-state NMR and high-resolution cryo-electron microscopy to determine the atomic structure of the helical RIP2 CARD filament, which reveals the intermolecular interactions that stabilize the assembly. Using structure-guided mutagenesis, we demonstrate the importance of RIP2 polymerization for the activation of NF-κB signalling by NOD2. Our results could be of use to develop new pharmacological strategies to treat inflammatory diseases characterised by aberrant NOD2 signalling. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_4399.map.gz | 1.7 MB | EMDB map data format | |
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Header (meta data) | emd-4399-v30.xml emd-4399.xml | 9.8 KB 9.8 KB | Display Display | EMDB header |
Images | emd_4399.png | 72.3 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-4399 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-4399 | HTTPS FTP |
-Related structure data
Related structure data | 6ggsMC 6gfjC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_4399.map.gz / Format: CCP4 / Size: 3.8 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Voxel size | X=Y=Z: 1.21 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : Helical assemble of the CARD domain of RIP2
Entire | Name: Helical assemble of the CARD domain of RIP2 |
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Components |
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-Supramolecule #1: Helical assemble of the CARD domain of RIP2
Supramolecule | Name: Helical assemble of the CARD domain of RIP2 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: escherichia coli (E. coli) |
-Macromolecule #1: Receptor-interacting serine/threonine-protein kinase 2
Macromolecule | Name: Receptor-interacting serine/threonine-protein kinase 2 type: protein_or_peptide / ID: 1 / Number of copies: 10 / Enantiomer: LEVO / EC number: non-specific serine/threonine protein kinase |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 12.572368 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: LQPGIAQQWI QSKREDIVNQ MTEACLNQSL DALLSRDLIM KEDYELVSTK PTRTSKVRQL LDTTDIQGEE FAKVIVQKLK DNKQMGLQP YPEILVVSRS PSLNLLQNKS M |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | helical reconstruction |
Aggregation state | helical array |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI POLARA 300 |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy |
Image recording | Film or detector model: GATAN K2 QUANTUM (4k x 4k) / Average electron dose: 1.25 e/Å2 |
Experimental equipment | Model: Tecnai Polara / Image courtesy: FEI Company |
-Image processing
Final angle assignment | Type: NOT APPLICABLE |
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Final reconstruction | Applied symmetry - Helical parameters - Δz: 4.848 Å Applied symmetry - Helical parameters - Δ&Phi: -101.12 ° Applied symmetry - Helical parameters - Axial symmetry: C1 (asymmetric) Resolution.type: BY AUTHOR / Resolution: 3.94 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: SPRING / Number images used: 9661 |