+Open data
-Basic information
Entry | Database: PDB / ID: 2mb9 | ||||||
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Title | Human Bcl10 CARD | ||||||
Components | B-cell lymphoma/leukemia 10 | ||||||
Keywords | SIGNALING PROTEIN / Death domain / APOPTOSIS | ||||||
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 | SOLUTION NMR / simulated annealing | ||||||
Model details | closest to the average, model10 | ||||||
Authors | Zheng, C. / Bracken, C. / Wu, H. | ||||||
Citation | Journal: Mol Cell / Year: 2013 Title: Structural architecture of the CARMA1/Bcl10/MALT1 signalosome: nucleation-induced filamentous assembly. Authors: Qi Qiao / Chenghua Yang / Chao Zheng / Lorena Fontán / Liron David / Xiong Yu / Clay Bracken / Monica Rosen / Ari Melnick / Edward H Egelman / Hao Wu / Abstract: The CARMA1/Bcl10/MALT1 (CBM) signalosome mediates antigen receptor-induced NF-κB signaling to regulate multiple lymphocyte functions. While CARMA1 and Bcl10 contain caspase recruitment domains ...The CARMA1/Bcl10/MALT1 (CBM) signalosome mediates antigen receptor-induced NF-κB signaling to regulate multiple lymphocyte functions. While CARMA1 and Bcl10 contain caspase recruitment domains (CARDs), MALT1 is a paracaspase with structural similarity to caspases. Here we show that the reconstituted CBM signalosome is a helical filamentous assembly in which substoichiometric CARMA1 nucleates Bcl10 filaments. Bcl10 filament formation is a highly cooperative process whose threshold is sensitized by oligomerized CARMA1 upon receptor activation. In cells, both cotransfected CARMA1/Bcl10 complex and the endogenous CBM signalosome are filamentous morphologically. Combining crystallography, nuclear magnetic resonance, and electron microscopy, we reveal the structure of the Bcl10 CARD filament and the mode of interaction between CARMA1 and Bcl10. Structure-guided mutagenesis confirmed the observed interfaces in Bcl10 filament assembly and MALT1 activation in vitro and NF-κB activation in cells. These data support a paradigm of nucleation-induced signal transduction with threshold response due to cooperativity and signal amplification by polymerization. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 2mb9.cif.gz | 357.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb2mb9.ent.gz | 297.1 KB | Display | PDB format |
PDBx/mmJSON format | 2mb9.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/mb/2mb9 ftp://data.pdbj.org/pub/pdb/validation_reports/mb/2mb9 | HTTPS FTP |
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-Related structure data
-Links
-Assembly
Deposited unit |
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1 |
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NMR ensembles |
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-Components
#1: Protein | Mass: 13852.984 Da / Num. of mol.: 1 / Fragment: CARD domain residues 1-115 / Mutation: E53R 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: SOLUTION NMR |
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NMR experiment | Type: 2D 1H-15N HSQC |
-Sample preparation
Details | Contents: 0.3-0.4 mM [U-13C; U-15N] Bcl10, 93% H2O/7% D2O / Solvent system: 93% H2O/7% D2O |
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Sample | Units: mM / Component: Bcl10-1 / Isotopic labeling: [U-13C; U-15N] / Conc. range: 0.3-0.4 |
Sample conditions | Ionic strength: 0.05 / pH: 6.5 / Pressure: ambient / Temperature: 300 K |
-NMR measurement
NMR spectrometer | Type: Varian Unity / Manufacturer: Varian / Model: UNITY / Field strength: 600 MHz |
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-Processing
NMR software |
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Refinement | Method: simulated annealing / Software ordinal: 1 | ||||||||||||
NMR representative | Selection criteria: closest to the average | ||||||||||||
NMR ensemble | Conformer selection criteria: structures with the lowest energy Conformers calculated total number: 1000 / Conformers submitted total number: 10 |