+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-8625 | |||||||||
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Title | Cryo-EM structure of the MAL TIR domain filament | |||||||||
Map data | Cryo-EM structure of the MAL TIR domain filament | |||||||||
Sample |
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Function / homology | Function and homology information positive regulation of interleukin-15 production / TIRAP-dependent toll-like receptor 4 signaling pathway / regulation of interferon-beta production / cellular response to bacterial lipopeptide / positive regulation of toll-like receptor 3 signaling pathway / Toll-like receptor 4 binding / positive regulation of toll-like receptor 2 signaling pathway / Toll-like receptor 2 binding / positive regulation of toll-like receptor 4 signaling pathway / positive regulation of chemokine (C-X-C motif) ligand 1 production ...positive regulation of interleukin-15 production / TIRAP-dependent toll-like receptor 4 signaling pathway / regulation of interferon-beta production / cellular response to bacterial lipopeptide / positive regulation of toll-like receptor 3 signaling pathway / Toll-like receptor 4 binding / positive regulation of toll-like receptor 2 signaling pathway / Toll-like receptor 2 binding / positive regulation of toll-like receptor 4 signaling pathway / positive regulation of chemokine (C-X-C motif) ligand 1 production / myeloid cell differentiation / positive regulation of chemokine (C-X-C motif) ligand 2 production / positive regulation of neutrophil chemotaxis / MyD88 deficiency (TLR2/4) / MyD88-dependent toll-like receptor 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 / regulation of innate immune response / extrinsic component of cytoplasmic side of plasma membrane / cellular response to lipoteichoic acid / endocytic vesicle / signaling adaptor activity / positive regulation of B cell proliferation / phosphatidylinositol-4,5-bisphosphate binding / positive regulation of interleukin-12 production / positive regulation of interleukin-8 production / protein kinase C binding / positive regulation of JNK cascade / ruffle membrane / positive regulation of protein-containing complex assembly / positive regulation of interleukin-6 production / positive regulation of tumor necrosis factor production / positive regulation of NF-kappaB transcription factor activity / protein-macromolecule adaptor activity / positive regulation of canonical NF-kappaB signal transduction / ER-Phagosome pathway / response to lipopolysaccharide / positive regulation of ERK1 and ERK2 cascade / cell surface receptor signaling pathway / molecular adaptor activity / defense response to Gram-positive bacterium / inflammatory response / innate immune response / cell surface / identical protein binding / plasma membrane / cytoplasm / cytosol Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | helical reconstruction / cryo EM / Resolution: 7.0 Å | |||||||||
Authors | Ve T / Vajjhala PR / Hedger A / Croll T / DiMaio F / Horsefield S / Yu X / Lavrencic P / Hassan Z / Morgan GP ...Ve T / Vajjhala PR / Hedger A / Croll T / DiMaio F / Horsefield S / Yu X / Lavrencic P / Hassan Z / Morgan GP / Mansell A / Mobli M / O'Carrol A / Chauvin B / Gambin Y / Sierecki E / Landsberg MJ / Stacey KJ / Egelman EH / Kobe B | |||||||||
Funding support | Australia, 1 items
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Citation | Journal: Nat Struct Mol Biol / Year: 2017 Title: Structural basis of TIR-domain-assembly formation in MAL- and MyD88-dependent TLR4 signaling. Authors: Thomas Ve / Parimala R Vajjhala / Andrew Hedger / Tristan Croll / Frank DiMaio / Shane Horsefield / Xiong Yu / Peter Lavrencic / Zahid Hassan / Garry P Morgan / Ashley Mansell / Mehdi Mobli ...Authors: Thomas Ve / Parimala R Vajjhala / Andrew Hedger / Tristan Croll / Frank DiMaio / Shane Horsefield / Xiong Yu / Peter Lavrencic / Zahid Hassan / Garry P Morgan / Ashley Mansell / Mehdi Mobli / Ailis O'Carroll / Brieuc Chauvin / Yann Gambin / Emma Sierecki / Michael J Landsberg / Katryn J Stacey / Edward H Egelman / Bostjan Kobe / Abstract: Toll-like receptor (TLR) signaling is a key innate immunity response to pathogens. Recruitment of signaling adapters such as MAL (TIRAP) and MyD88 to the TLRs requires Toll/interleukin-1 receptor ...Toll-like receptor (TLR) signaling is a key innate immunity response to pathogens. Recruitment of signaling adapters such as MAL (TIRAP) and MyD88 to the TLRs requires Toll/interleukin-1 receptor (TIR)-domain interactions, which remain structurally elusive. Here we show that MAL TIR domains spontaneously and reversibly form filaments in vitro. They also form cofilaments with TLR4 TIR domains and induce formation of MyD88 assemblies. A 7-Å-resolution cryo-EM structure reveals a stable MAL protofilament consisting of two parallel strands of TIR-domain subunits in a BB-loop-mediated head-to-tail arrangement. Interface residues that are important for the interaction are conserved among different TIR domains. Although large filaments of TLR4, MAL or MyD88 are unlikely to form during cellular signaling, structure-guided mutagenesis, combined with in vivo interaction assays, demonstrated that the MAL interactions defined within the filament represent a template for a conserved mode of TIR-domain interaction involved in both TLR and interleukin-1 receptor signaling. | |||||||||
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_8625.map.gz | 5.9 MB | EMDB map data format | |
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Header (meta data) | emd-8625-v30.xml emd-8625.xml | 11.4 KB 11.4 KB | Display Display | EMDB header |
Images | emd_8625.png | 77.8 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-8625 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-8625 | HTTPS FTP |
-Validation report
Summary document | emd_8625_validation.pdf.gz | 368.4 KB | Display | EMDB validaton report |
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Full document | emd_8625_full_validation.pdf.gz | 367.9 KB | Display | |
Data in XML | emd_8625_validation.xml.gz | 5.1 KB | Display | |
Data in CIF | emd_8625_validation.cif.gz | 5.6 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-8625 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-8625 | HTTPS FTP |
-Related structure data
Related structure data | 5uzbMC 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_8625.map.gz / Format: CCP4 / Size: 25.8 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Cryo-EM structure of the MAL TIR domain filament | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.07 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 : MAL TIR domain filament
Entire | Name: MAL TIR domain filament |
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Components |
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-Supramolecule #1: MAL TIR domain filament
Supramolecule | Name: MAL TIR domain filament / 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: Toll/interleukin-1 receptor domain-containing adapter protein
Macromolecule | Name: Toll/interleukin-1 receptor domain-containing adapter protein type: protein_or_peptide / ID: 1 / Number of copies: 14 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 19.689162 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: MHHHHHHSSG VDLGTENLYF QSNAEQKLIS EEDLSSRWSK DYDVCVCHSE EDLVAAQDLV SYLEGSTASL RCFLQLRDAT PGGAIVSEL CQALSSSHCR VLLITPGFLQ DPWCKYQMLQ ALTEAPGAEG CTIPLLSGLS RAAYPPELRF MYYVDGRGPD G GFRQVKEA VMRYLQTLS |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | helical reconstruction |
Aggregation state | filament |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: FEI FALCON II (4k x 4k) / Number real images: 446 / Average electron dose: 20.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Final reconstruction | Applied symmetry - Helical parameters - Δz: 15.5 Å Applied symmetry - Helical parameters - Δ&Phi: -26.8 ° Applied symmetry - Helical parameters - Axial symmetry: C6 (6 fold cyclic) Resolution.type: BY AUTHOR / Resolution: 7.0 Å / Resolution method: OTHER / Software: (Name: SPIDER, IHRSR) / Number images used: 17175 |
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CTF correction | Software - Name: CTFFIND3 |
Final angle assignment | Type: NOT APPLICABLE |