+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-4405 | |||||||||
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Title | Helical MyD88 death domain filament | |||||||||
Map data | ||||||||||
Sample |
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Keywords | helix / filament / TLR / SIGNALING PROTEIN | |||||||||
Function / homology | Function and homology information regulation of chemokine (C-X-C motif) ligand 1 production / neutrophil-mediated killing of bacterium / MyD88 deficiency (TLR5) / regulation of chemokine (C-X-C motif) ligand 2 production / ATP-dependent histone chaperone activity / Toll binding / induced systemic resistance / leukocyte activation involved in inflammatory response / TIR domain binding / response to molecule of fungal origin ...regulation of chemokine (C-X-C motif) ligand 1 production / neutrophil-mediated killing of bacterium / MyD88 deficiency (TLR5) / regulation of chemokine (C-X-C motif) ligand 2 production / ATP-dependent histone chaperone activity / Toll binding / induced systemic resistance / leukocyte activation involved in inflammatory response / TIR domain binding / response to molecule of fungal origin / toll-like receptor 8 signaling pathway / positive regulation of lymphocyte proliferation / response to peptidoglycan / establishment of endothelial intestinal barrier / positive regulation of interleukin-23 production / MyD88 dependent cascade initiated on endosome / IRAK4 deficiency (TLR5) / TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation / regulation of neutrophil migration / MyD88 cascade initiated on plasma membrane / cellular response to oxidised low-density lipoprotein particle stimulus / Toll signaling pathway / Toll-like receptor binding / DEx/H-box helicases activate type I IFN and inflammatory cytokines production / interleukin-33-mediated signaling pathway / neutrophil activation involved in immune response / microglia differentiation / interleukin-1 receptor binding / RIP-mediated NFkB activation via ZBP1 / positive regulation of cytokine production involved in inflammatory response / death receptor binding / MyD88 deficiency (TLR2/4) / interleukin-1-mediated signaling pathway / MyD88-dependent toll-like receptor signaling pathway / positive regulation of macrophage cytokine production / IRAK4 deficiency (TLR2/4) / MyD88:MAL(TIRAP) cascade initiated on plasma membrane / toll-like receptor 4 signaling pathway / 3'-UTR-mediated mRNA stabilization / skin development / extrinsic component of plasma membrane / positive regulation of NLRP3 inflammasome complex assembly / immune system process / type I interferon-mediated signaling pathway / defense response to protozoan / response to amine / positive regulation of interleukin-17 production / extrinsic component of cytoplasmic side of plasma membrane / positive regulation of type I interferon production / response to amino acid / immunoglobulin mediated immune response / phagocytosis / signaling adaptor activity / lipopolysaccharide-mediated signaling pathway / positive regulation of chemokine production / JNK cascade / p75NTR recruits signalling complexes / TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling / response to interleukin-1 / positive regulation of interleukin-1 beta production / positive regulation of interleukin-8 production / positive regulation of JNK cascade / positive regulation of smooth muscle cell proliferation / response to organic cyclic compound / cellular response to mechanical stimulus / positive regulation of interleukin-6 production / Interleukin-1 signaling / positive regulation of tumor necrosis factor production / PIP3 activates AKT signaling / positive regulation of NF-kappaB transcription factor activity / ER-Phagosome pathway / regulation of inflammatory response / gene expression / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / cellular response to lipopolysaccharide / defense response to virus / positive regulation of canonical NF-kappaB signal transduction / response to ethanol / molecular adaptor activity / cell surface receptor signaling pathway / endosome membrane / defense response to Gram-positive bacterium / defense response to bacterium / inflammatory response / innate immune response / positive regulation of gene expression / apoptotic process / cell surface / signal transduction / positive regulation of transcription by RNA polymerase II / protein-containing complex / identical protein binding / nucleus / plasma membrane / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | helical reconstruction / cryo EM / Resolution: 3.1 Å | |||||||||
Authors | Moncrieffe MC / Bollschweiler D | |||||||||
Citation | Journal: Structure / Year: 2020 Title: MyD88 Death-Domain Oligomerization Determines Myddosome Architecture: Implications for Toll-like Receptor Signaling. Authors: Martin C Moncrieffe / Daniel Bollschweiler / Bing Li / Pawel A Penczek / Lee Hopkins / Clare E Bryant / David Klenerman / Nicholas J Gay / Abstract: Toll-like receptors (TLRs) are pivotal in triggering the innate immune response to pathogen infection. Ligand binding induces receptor dimerization which facilitates the recruitment of other post- ...Toll-like receptors (TLRs) are pivotal in triggering the innate immune response to pathogen infection. Ligand binding induces receptor dimerization which facilitates the recruitment of other post-receptor signal transducers into a complex signalosome, the Myddosome. Central to this process is Myeloid differentiation primary response 88 (MyD88), which is required by almost all TLRs, and signaling is thought to proceed via the stepwise, sequential assembly of individual components. Here, we show that the death domains of human MyD88 spontaneously and reversibly associate to form helical filaments in vitro. A 3.1-Å cryoelectron microscopy structure reveals that the architecture of the filament is identical to that of the 6:4 MyD88-IRAK4-IRAK2 hetero-oligomeric Myddosome. Additionally, the death domain of IRAK4 interacts with the filaments to reconstitute the non-stoichiometric 6:4 MyD88-IRAK4 complex. Together, these data suggest that intracellularly, the MyD88 scaffold may be pre-formed and poised for recruitment of IRAKs on receptor activation and TIR engagement. | |||||||||
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_4405.map.gz | 37.7 MB | EMDB map data format | |
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Header (meta data) | emd-4405-v30.xml emd-4405.xml | 15.7 KB 15.7 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_4405_fsc.xml | 7.9 KB | Display | FSC data file |
Images | emd_4405.png | 98.2 KB | ||
Masks | emd_4405_msk_1.map | 40.6 MB | Mask map | |
Filedesc metadata | emd-4405.cif.gz | 5.7 KB | ||
Others | emd_4405_half_map_1.map.gz emd_4405_half_map_2.map.gz | 31.2 MB 31.2 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-4405 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-4405 | HTTPS FTP |
-Validation report
Summary document | emd_4405_validation.pdf.gz | 442 KB | Display | EMDB validaton report |
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Full document | emd_4405_full_validation.pdf.gz | 441.1 KB | Display | |
Data in XML | emd_4405_validation.xml.gz | 13.6 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-4405 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-4405 | HTTPS FTP |
-Related structure data
Related structure data | 6i3nMC 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_4405.map.gz / Format: CCP4 / Size: 40.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.06 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Mask #1
File | emd_4405_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_4405_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_4405_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Human MyD88
Entire | Name: Human MyD88 |
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Components |
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-Supramolecule #1: Human MyD88
Supramolecule | Name: Human MyD88 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Myeloid differentiation primary response protein MyD88
Macromolecule | Name: Myeloid differentiation primary response protein MyD88 type: protein_or_peptide / ID: 1 / Number of copies: 13 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 17.646873 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: SNAMAAGGPG AGSAAPVSST SSLPLAALNM RVRRRLSLFL NVRTQVAADW TALAEEMDFE YLEIRQLETQ ADPTGRLLDA WQGRPGASV GRLLELLTKL GRDDVLLELG PSIEEDCQKY ILKQQQEEAE KPLQVAAVDS SVPRTAELAG ITTLDWSHPQ F EK UniProtKB: Myeloid differentiation primary response protein MyD88 |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | helical reconstruction |
Aggregation state | filament |
-Sample preparation
Buffer | pH: 8 Component:
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Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Support film - Material: CARBON / Support film - topology: HOLEY | |||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: FEI FALCON III (4k x 4k) / Detector mode: INTEGRATING / Average electron dose: 0.92 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 50.0 µm / Calibrated defocus max: 3.2 µm / Calibrated defocus min: 0.9 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 3.1 µm / Nominal defocus min: 1.0 µm / Nominal magnification: 75000 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |