6GK2

Helical reconstruction of BCL10 CARD and MALT1 DEATH DOMAIN complex

Summary for 6GK2

• Entry DOI: 10.2210/pdb6gk2/pdb
• EMDB information: 0013
• Descriptor: B-cell lymphoma/leukemia 10, Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (2 entities in total)
• Functional Keywords: bcl10, malt1, cbm complex, helical reconstruction, cancer, autoimmune disease, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 23015.69

Authors

Schlauderer, F.,Desfosses, A.,Gutsche, I.,Hopfner, K.P.,Lammens, K. (deposition date: 2018-05-18, release date: 2018-10-31, Last modification date: 2024-11-06)

Primary citation

Schlauderer, F.,Seeholzer, T.,Desfosses, A.,Gehring, T.,Strauss, M.,Hopfner, K.P.,Gutsche, I.,Krappmann, D.,Lammens, K.
Molecular architecture and regulation of BCL10-MALT1 filaments.
Nat Commun, 9:4041-4041, 2018

PubMed Abstract: The CARD11-BCL10-MALT1 (CBM) complex triggers the adaptive immune response in lymphocytes and lymphoma cells. CARD11/CARMA1 acts as a molecular seed inducing BCL10 filaments, but the integration of MALT1 and the assembly of a functional CBM complex has remained elusive. Using cryo-EM we solved the helical structure of the BCL10-MALT1 filament. The structural model of the filament core solved at 4.9 Å resolution identified the interface between the N-terminal MALT1 DD and the BCL10 caspase recruitment domain. The C-terminal MALT1 Ig and paracaspase domains protrude from this core to orchestrate binding of mediators and substrates at the filament periphery. Mutagenesis studies support the importance of the identified BCL10-MALT1 interface for CBM complex assembly, MALT1 protease activation and NF-κB signaling in Jurkat and primary CD4 T-cells. Collectively, we present a model for the assembly and architecture of the CBM signaling complex and how it functions as a signaling hub in T-lymphocytes.

PubMed: 30279415
DOI: 10.1038/s41467-018-06573-8

Experimental method

ELECTRON MICROSCOPY (4.9 Å)