2MB9

Human Bcl10 CARD


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 1000 
  • Conformers Submitted: 10 
  • Selection Criteria: structures with the lowest energy 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Structural Architecture of the CARMA1/Bcl10/MALT1 Signalosome: Nucleation-Induced Filamentous Assembly.

Qiao, Q.Yang, C.Zheng, C.Fontan, L.David, L.Yu, X.Bracken, C.Rosen, M.Melnick, A.Egelman, E.H.Wu, H.

(2013) Mol Cell 51: 766-779

  • DOI: https://doi.org/10.1016/j.molcel.2013.08.032
  • Primary Citation of Related Structures:  
    2MB9, 4LWD

  • PubMed 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 (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.


  • Organizational Affiliation

    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
B-cell lymphoma/leukemia 10118Homo sapiensMutation(s): 1 
Gene Names: BCL10CIPERCLAP
UniProt & NIH Common Fund Data Resources
Find proteins for O95999 (Homo sapiens)
Explore O95999 
Go to UniProtKB:  O95999
PHAROS:  O95999
GTEx:  ENSG00000142867 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO95999
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 1000 
  • Conformers Submitted: 10 
  • Selection Criteria: structures with the lowest energy 

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-10-16
    Type: Initial release
  • Version 1.1: 2023-06-14
    Changes: Database references, Other
  • Version 1.2: 2024-05-15
    Changes: Data collection, Database references