+Open data
-Basic information
Entry | Database: PDB / ID: 6i3n | ||||||
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Title | Helical MyD88 death domain filament | ||||||
Components | Myeloid differentiation primary response protein MyD88 | ||||||
Keywords | SIGNALING PROTEIN / helix / filament / TLR | ||||||
Function / homology | Function and homology information regulation of chemokine (C-X-C motif) ligand 1 production / Toll binding / MyD88 deficiency (TLR5) / regulation of chemokine (C-X-C motif) ligand 2 production / ATP-dependent histone chaperone activity / neutrophil-mediated killing of bacterium / 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 / Toll binding / MyD88 deficiency (TLR5) / regulation of chemokine (C-X-C motif) ligand 2 production / ATP-dependent histone chaperone activity / neutrophil-mediated killing of bacterium / 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 / positive regulation of interleukin-23 production / establishment of endothelial intestinal barrier / IRAK4 deficiency (TLR5) / regulation of neutrophil migration / cellular response to oxidised low-density lipoprotein particle stimulus / MyD88 dependent cascade initiated on endosome / TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation / MyD88 cascade initiated on plasma membrane / Toll signaling pathway / Toll-like receptor binding / DEx/H-box helicases activate type I IFN and inflammatory cytokines production / neutrophil activation involved in immune response / interleukin-33-mediated signaling pathway / microglia differentiation / RIP-mediated NFkB activation via ZBP1 / positive regulation of cytokine production involved in inflammatory response / interleukin-1 receptor binding / death receptor binding / MyD88 deficiency (TLR2/4) / positive regulation of macrophage cytokine production / MyD88-dependent toll-like receptor signaling pathway / interleukin-1-mediated signaling pathway / 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 / positive regulation of NLRP3 inflammasome complex assembly / immune system process / extrinsic component of plasma membrane / type I interferon-mediated signaling pathway / positive regulation of interleukin-17 production / defense response to protozoan / response to amine / immunoglobulin mediated immune response / positive regulation of type I interferon production / response to amino acid / phagocytosis / signaling adaptor activity / positive regulation of chemokine production / JNK cascade / lipopolysaccharide-mediated signaling pathway / extrinsic component of cytoplasmic side of plasma membrane / 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 / Interleukin-1 signaling / cellular response to mechanical stimulus / positive regulation of interleukin-6 production / positive regulation of tumor necrosis factor production / : / PIP3 activates AKT signaling / positive regulation of NF-kappaB transcription factor activity / gene expression / ER-Phagosome pathway / regulation of inflammatory response / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / cellular response to lipopolysaccharide / positive regulation of canonical NF-kappaB signal transduction / response to ethanol / defense response to virus / 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 / apoptotic process / positive regulation of gene expression / cell surface / signal transduction / positive regulation of transcription by RNA polymerase II / protein-containing complex / identical protein binding / nucleus / plasma membrane / cytoplasm / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / helical reconstruction / cryo EM / Resolution: 3.1 Å | ||||||
Authors | Moncrieffe, M.C. / Bollschweiler, D. / Penczek, P.A.P. / Gay, N.J. | ||||||
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 | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6i3n.cif.gz | 242.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6i3n.ent.gz | 194 KB | Display | PDB format |
PDBx/mmJSON format | 6i3n.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6i3n_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 6i3n_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 6i3n_validation.xml.gz | 37.8 KB | Display | |
Data in CIF | 6i3n_validation.cif.gz | 61.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/i3/6i3n ftp://data.pdbj.org/pub/pdb/validation_reports/i3/6i3n | HTTPS FTP |
-Related structure data
Related structure data | 4405MC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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-Components
#1: Protein | Mass: 17646.873 Da / Num. of mol.: 13 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: MYD88 / Production host: Escherichia coli (E. coli) / References: UniProt: H0Y4G9, UniProt: Q99836*PLUS |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: FILAMENT / 3D reconstruction method: helical reconstruction |
-Sample preparation
Component | Name: Human MyD88 / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT | |||||||||||||||
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Source (natural) | Organism: Homo sapiens (human) | |||||||||||||||
Source (recombinant) | Organism: Escherichia coli (E. coli) | |||||||||||||||
Buffer solution | pH: 8 | |||||||||||||||
Buffer component |
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Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | |||||||||||||||
Specimen support | Grid material: COPPER / Grid type: Quantifoil R1.2/1.3 | |||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 75000 X / Nominal defocus max: 3100 nm / Nominal defocus min: 1000 nm / Calibrated defocus min: 900 nm / Calibrated defocus max: 3200 nm / Cs: 2.7 mm / C2 aperture diameter: 50 µm |
Image recording | Electron dose: 0.92 e/Å2 / Detector mode: INTEGRATING / Film or detector model: FEI FALCON III (4k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.14rc2_3191: / Classification: refinement | ||||||||||||||||||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||
Helical symmerty | Angular rotation/subunit: 98.01 ° / Axial rise/subunit: 5.98 Å / Axial symmetry: C1 | ||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 1229488 / Symmetry type: HELICAL | ||||||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: OTHER | ||||||||||||||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 3MOP Pdb chain-ID: A / Accession code: 3MOP / Source name: PDB / Type: experimental model |