Molecular architecture and regulation of BCL10-MALT1 filaments

Florian Schlauderer (1) , Thomas Seeholzer (2) , Ambroise Desfosses (3) , Torben Gehring (4) , Mike Strauss (5) , Karl-Peter Hopfner (1) , Irina Gutsche (3) , Daniel Krappmann (6) , Katja Lammens (1)

1 Gene Center
2 Research Unit Cellular Signal Integration
3 IBS - UMR 5075 - Institut de biologie structurale
4 Research Unit Cellular Signal Integration
5 Department of Anatomy and Cell Biology [Montréal]
6 Research Unit Cellular Signal Integration

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.

Domaines: Biologie structurale [q-bio.BM]

Florian Schlauderer, Thomas Seeholzer, Ambroise Desfosses, Torben Gehring, Mike Strauss, et al.. Molecular architecture and regulation of BCL10-MALT1 filaments. Nature Communications, 2018, 9 (1), pp.4041. ⟨10.1038/s41467-018-06573-8⟩. ⟨hal-01987271⟩