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- PDB-2mb9: Human Bcl10 CARD -

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Basic information

Entry
Database: PDB / ID: 2mb9
TitleHuman Bcl10 CARD
ComponentsB-cell lymphoma/leukemia 10
KeywordsSIGNALING 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
B-cell lymphoma/leukemia 10/E10 / BCL10, CARD domain / Death Domain, Fas / Death Domain, Fas / CARD domain / CARD caspase recruitment domain profile. / Caspase recruitment domain / Death-like domain superfamily / Orthogonal Bundle / Mainly Alpha
Similarity search - Domain/homology
B-cell lymphoma/leukemia 10
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodSOLUTION NMR / simulated annealing
Model detailsclosest to the average, model10
AuthorsZheng, C. / Bracken, C. / Wu, H.
CitationJournal: 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
DepositionJul 26, 2013Deposition site: BMRB / Processing site: RCSB
Revision 1.0Oct 16, 2013Provider: repository / Type: Initial release
Revision 1.1Jun 14, 2023Group: Database references / Other
Category: database_2 / pdbx_database_status / struct_ref_seq_dif
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_database_status.status_code_nmr_data / _struct_ref_seq_dif.details

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
A: B-cell lymphoma/leukemia 10


Theoretical massNumber of molelcules
Total (without water)13,8531
Polymers13,8531
Non-polymers00
Water0
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
NMR ensembles
DataCriteria
Number of conformers (submitted / calculated)10 / 1000structures with the lowest energy
RepresentativeModel #1closest to the average

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Components

#1: Protein B-cell lymphoma/leukemia 10 / B-cell CLL/lymphoma 10 / Bcl-10 / CARD-containing molecule enhancing NF-kappa-B / CARD-like ...B-cell CLL/lymphoma 10 / Bcl-10 / CARD-containing molecule enhancing NF-kappa-B / CARD-like apoptotic protein / hCLAP / CED-3/ICH-1 prodomain homologous E10-like regulator / CIPER / Cellular homolog of vCARMEN / cCARMEN / Cellular-E10 / c-E10 / Mammalian CARD-containing adapter molecule E10 / mE10


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

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Experiment

ExperimentMethod: SOLUTION NMR
NMR experimentType: 2D 1H-15N HSQC

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Sample preparation

DetailsContents: 0.3-0.4 mM [U-13C; U-15N] Bcl10, 93% H2O/7% D2O / Solvent system: 93% H2O/7% D2O
SampleUnits: mM / Component: Bcl10-1 / Isotopic labeling: [U-13C; U-15N] / Conc. range: 0.3-0.4
Sample conditionsIonic strength: 0.05 / pH: 6.5 / Pressure: ambient / Temperature: 300 K

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NMR measurement

NMR spectrometerType: Varian Unity / Manufacturer: Varian / Model: UNITY / Field strength: 600 MHz

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Processing

NMR software
NameDeveloperClassification
CCPNMRCCPNchemical shift assignment
CNSBrunger, Adams, Clore, Gros, Nilges and Readstructure solution
CNSBrunger, Adams, Clore, Gros, Nilges and Readrefinement
RefinementMethod: simulated annealing / Software ordinal: 1
NMR representativeSelection criteria: closest to the average
NMR ensembleConformer selection criteria: structures with the lowest energy
Conformers calculated total number: 1000 / Conformers submitted total number: 10

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