[HTML][HTML] Molecular architecture and regulation of BCL10-MALT1 filaments

F Schlauderer, T Seeholzer, A Desfosses… - Nature …, 2018 - nature.com
F Schlauderer, T Seeholzer, A Desfosses, T Gehring, M Strauss, KP Hopfner, I Gutsche…
Nature communications, 2018nature.com
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 …
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.
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