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Yorodumi- PDB-7ber: SFX structure of the MyD88 TIR domain higher-order assembly (solv... -
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-Basic information
Entry | Database: PDB / ID: 7ber | |||||||||
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Title | SFX structure of the MyD88 TIR domain higher-order assembly (solved, rebuilt and refined using an identical protocol to the MicroED structure of the MyD88 TIR domain higher-order assembly) | |||||||||
Components | Myeloid differentiation primary response protein MyD88 | |||||||||
Keywords | PROTEIN BINDING / SFX / serial femtosecond crystallography / MyD88 / TIR domain / higher-order assembly | |||||||||
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 / regulation of neutrophil migration / IRAK4 deficiency (TLR5) / MyD88 dependent cascade initiated on endosome / cellular response to oxidised low-density lipoprotein particle stimulus / TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation / MyD88 cascade initiated on plasma membrane / Toll signaling pathway / DEx/H-box helicases activate type I IFN and inflammatory cytokines production / neutrophil activation involved in immune response / Toll-like receptor binding / 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 / skin development / 3'-UTR-mediated mRNA stabilization / positive regulation of NLRP3 inflammasome complex assembly / 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 / positive regulation of canonical NF-kappaB signal transduction / defense response to virus / response to ethanol / cellular response to lipopolysaccharide / molecular adaptor activity / cell surface receptor signaling pathway / endosome membrane / defense response to Gram-positive bacterium / defense response to bacterium / 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 / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | X-RAY DIFFRACTION / FREE ELECTRON LASER / MOLECULAR REPLACEMENT / Resolution: 2.3 Å | |||||||||
Authors | Clabbers, M.T.B. / Holmes, S. / Muusse, T.W. / Vajjhala, P. / Thygesen, S.J. / Malde, A.K. / Hunter, D.J.B. / Croll, T.I. / Nanson, J.D. / Rahaman, M.H. ...Clabbers, M.T.B. / Holmes, S. / Muusse, T.W. / Vajjhala, P. / Thygesen, S.J. / Malde, A.K. / Hunter, D.J.B. / Croll, T.I. / Nanson, J.D. / Rahaman, M.H. / Aquila, A. / Hunter, M.S. / Liang, M. / Yoon, C.H. / Zhao, J. / Zatsepin, N.A. / Abbey, B. / Sierecki, E. / Gambin, Y. / Darmanin, C. / Kobe, B. / Xu, H. / Ve, T. | |||||||||
Funding support | Sweden, Australia, 2items
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Citation | Journal: Nat Commun / Year: 2021 Title: MyD88 TIR domain higher-order assembly interactions revealed by microcrystal electron diffraction and serial femtosecond crystallography. Authors: Max T B Clabbers / Susannah Holmes / Timothy W Muusse / Parimala R Vajjhala / Sara J Thygesen / Alpeshkumar K Malde / Dominic J B Hunter / Tristan I Croll / Leonie Flueckiger / Jeffrey D ...Authors: Max T B Clabbers / Susannah Holmes / Timothy W Muusse / Parimala R Vajjhala / Sara J Thygesen / Alpeshkumar K Malde / Dominic J B Hunter / Tristan I Croll / Leonie Flueckiger / Jeffrey D Nanson / Md Habibur Rahaman / Andrew Aquila / Mark S Hunter / Mengning Liang / Chun Hong Yoon / Jingjing Zhao / Nadia A Zatsepin / Brian Abbey / Emma Sierecki / Yann Gambin / Katryn J Stacey / Connie Darmanin / Bostjan Kobe / Hongyi Xu / Thomas Ve / Abstract: MyD88 and MAL are Toll-like receptor (TLR) adaptors that signal to induce pro-inflammatory cytokine production. We previously observed that the TIR domain of MAL (MAL) forms filaments in vitro and ...MyD88 and MAL are Toll-like receptor (TLR) adaptors that signal to induce pro-inflammatory cytokine production. We previously observed that the TIR domain of MAL (MAL) forms filaments in vitro and induces formation of crystalline higher-order assemblies of the MyD88 TIR domain (MyD88). These crystals are too small for conventional X-ray crystallography, but are ideally suited to structure determination by microcrystal electron diffraction (MicroED) and serial femtosecond crystallography (SFX). Here, we present MicroED and SFX structures of the MyD88 assembly, which reveal a two-stranded higher-order assembly arrangement of TIR domains analogous to that seen previously for MAL. We demonstrate via mutagenesis that the MyD88 assembly interfaces are critical for TLR4 signaling in vivo, and we show that MAL promotes unidirectional assembly of MyD88. Collectively, our studies provide structural and mechanistic insight into TLR signal transduction and allow a direct comparison of the MicroED and SFX techniques. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7ber.cif.gz | 49.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7ber.ent.gz | 27.6 KB | Display | PDB format |
PDBx/mmJSON format | 7ber.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/be/7ber ftp://data.pdbj.org/pub/pdb/validation_reports/be/7ber | HTTPS FTP |
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-Related structure data
Related structure data | 7beqC 7l6wC 4w8gS S: Starting model for refinement C: citing same article (ref.) |
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Similar structure data | |
Experimental dataset #1 | Data reference: 10.11577/1767965 / Data set type: diffraction image data |
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
#1: Protein | Mass: 17833.854 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: MYD88 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: Q99836 |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.31 Å3/Da / Density % sol: 46.65 % |
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Crystal grow | Temperature: 310 K / Method: batch mode Details: MAL TIR (0.5-3 mM) incubated with MyD88 TIR (60-100 mM) in 10 mM HEPES pH 7.5-8, 150 mM NaCl at 310K |
-Data collection
Diffraction | Mean temperature: 300 K / Serial crystal experiment: N |
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Diffraction source | Source: FREE ELECTRON LASER / Site: SLAC LCLS / Beamline: CXI / Wavelength: 1.3 Å |
Detector | Type: CS-PAD CXI-1 / Detector: PIXEL / Date: Dec 17, 2015 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.3 Å / Relative weight: 1 |
Reflection | Resolution: 2.3→30.94 Å / Num. obs: 7118 / % possible obs: 95.8 % / Redundancy: 1 % / Biso Wilson estimate: 32.47 Å2 / CC1/2: 0.9 / Net I/σ(I): 2.6 |
Reflection shell | Resolution: 2.3→2.38 Å / Redundancy: 1 % / Mean I/σ(I) obs: 1.1 / Num. unique obs: 560 / CC1/2: 0.36 / % possible all: 78.1 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 4W8G Resolution: 2.3→30.93 Å / SU ML: 0.2669 / Cross valid method: THROUGHOUT / σ(F): 1.91 / Phase error: 39.873 / Stereochemistry target values: CDL v1.2
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | ||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 45.6 Å2 | ||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.3→30.93 Å
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Refine LS restraints |
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LS refinement shell |
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