+Open data
-Basic information
Entry | Database: PDB / ID: 6bze | ||||||
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Title | Cryo-EM structure of BCL10 CARD filament | ||||||
Components | B-cell lymphoma/leukemia 10 | ||||||
Keywords | SIGNALING PROTEIN / CARD / filament / signalosome / helical reconstruction | ||||||
Function / homology | Function and homology information positive regulation of lymphotoxin A production / polkadots / CBM complex / antifungal innate immune response / protein kinase B binding / T cell apoptotic process / positive regulation of mast cell cytokine production / CARD domain binding / programmed cell death / negative regulation of mature B cell apoptotic process ...positive regulation of lymphotoxin A production / polkadots / CBM complex / antifungal innate immune response / protein kinase B binding / T cell apoptotic process / positive regulation of mast cell cytokine production / CARD domain binding / programmed cell death / negative regulation of mature B cell apoptotic process / B cell apoptotic process / positive regulation of extrinsic apoptotic signaling pathway / response to food / toll-like receptor signaling pathway / positive regulation of T cell receptor signaling pathway / non-canonical NF-kappaB signal transduction / positive regulation of cysteine-type endopeptidase activity involved in apoptotic process / immunoglobulin mediated immune response / immunological synapse / general transcription initiation factor binding / NF-kappaB binding / canonical NF-kappaB signal transduction / cellular defense response / cytoplasmic microtubule / positive regulation of phosphorylation / lipopolysaccharide-mediated signaling pathway / positive regulation of protein ubiquitination / neural tube closure / positive regulation of interleukin-8 production / Activation of NF-kappaB in B cells / protein homooligomerization / CLEC7A (Dectin-1) signaling / FCERI mediated NF-kB activation / positive regulation of interleukin-6 production / cellular response to mechanical stimulus / : / positive regulation of T cell activation / Downstream TCR signaling / E3 ubiquitin ligases ubiquitinate target proteins / positive regulation of NF-kappaB transcription factor activity / T cell receptor signaling pathway / positive regulation of canonical NF-kappaB signal transduction / cellular response to lipopolysaccharide / protease binding / adaptive immune response / lysosome / transcription coactivator activity / positive regulation of apoptotic process / membrane raft / innate immune response / ubiquitin protein ligase binding / protein-containing complex binding / perinuclear region of cytoplasm / positive regulation of DNA-templated transcription / protein-containing complex / identical protein binding / nucleus / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / helical reconstruction / cryo EM / Resolution: 4 Å | ||||||
Authors | David, L. / Li, Y. / Ma, J. / Garner, E. / Zhang, X. / Wu, H. | ||||||
Funding support | United States, 1items
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Citation | Journal: Proc Natl Acad Sci U S A / Year: 2018 Title: Assembly mechanism of the CARMA1-BCL10-MALT1-TRAF6 signalosome. Authors: Liron David / Yang Li / Jun Ma / Ethan Garner / Xinzheng Zhang / Hao Wu / Abstract: The CARMA1-BCL10-MALT1 (CBM) signalosome is a central mediator of T cell receptor and B cell receptor-induced NF-κB signaling that regulates multiple lymphocyte functions. While caspase-recruitment ...The CARMA1-BCL10-MALT1 (CBM) signalosome is a central mediator of T cell receptor and B cell receptor-induced NF-κB signaling that regulates multiple lymphocyte functions. While caspase-recruitment domain (CARD) membrane-associated guanylate kinase (MAGUK) protein 1 (CARMA1) nucleates B cell lymphoma 10 (BCL10) filament formation through interactions between CARDs, mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is a paracaspase with structural similarity to caspases, which recruits TNF receptor-associated factor 6 (TRAF6) for K63-linked polyubiquitination. Here we present cryo-electron microscopy (cryo-EM) structure of the BCL10 CARD filament at 4.0-Å resolution. The structure redefines CARD-CARD interactions compared with the previous EM structure determined from a negatively stained sample. Surprisingly, time-lapse confocal imaging shows that BCL10 polymerizes in a unidirectional manner. CARMA1, the BCL10 nucleator, serves as a hub for formation of star-shaped filamentous networks of BCL10 and significantly decreases the lag period of BCL10 polymerization. Cooperative MALT1 interaction with BCL10 filaments observed under EM suggests immediate dimerization of MALT1 in the BCL10 filamentous scaffold. In addition, TRAF6 cooperatively decorates CBM filaments to form higher-order assemblies, likely resulting in all-or-none activation of the downstream pathway. Collectively, these data reveal biophysical mechanisms in the assembly of the CARMA1-BCL10-MALT1-TRAF6 complex for signal transduction. | ||||||
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 | 6bze.cif.gz | 379.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6bze.ent.gz | 318.5 KB | Display | PDB format |
PDBx/mmJSON format | 6bze.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/bz/6bze ftp://data.pdbj.org/pub/pdb/validation_reports/bz/6bze | HTTPS FTP |
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-Related structure data
Related structure data | 7314MC 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: 12614.566 Da / Num. of mol.: 8 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: BCL10, CIPER, CLAP / Production host: Escherichia coli (E. coli) / References: UniProt: O95999 |
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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: BCL10 CARD / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT | ||||||||||||||||||||
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Molecular weight | Experimental value: NO | ||||||||||||||||||||
Source (natural) | Organism: Homo sapiens (human) | ||||||||||||||||||||
Source (recombinant) | Organism: Escherichia coli (E. coli) | ||||||||||||||||||||
Buffer solution | pH: 7.5 | ||||||||||||||||||||
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 mesh size: 400 divisions/in. / Grid type: C-flat-1.2/1.3 4C | ||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK III / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 278 K / Details: 5 second blotting time with force 3 |
-Electron microscopy imaging
Experimental equipment | Model: Talos Arctica / Image courtesy: FEI Company |
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Microscopy | Model: FEI TECNAI ARCTICA |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 6000 nm / Nominal defocus min: 1000 nm / Cs: 2.7 mm / Alignment procedure: COMA FREE |
Image recording | Electron dose: 40 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: DIRECT ELECTRON DE-16 (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 339 |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||
Helical symmerty | Angular rotation/subunit: -100.8 ° / Axial rise/subunit: 5 Å / Axial symmetry: C1 | ||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 103873 | ||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 39992 / Symmetry type: HELICAL | ||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: RIGID BODY FIT | ||||||||||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 2MB9 Pdb chain-ID: A / Accession code: 2MB9 / Pdb chain residue range: 10-115 / Source name: PDB / Type: experimental model |