Molecular architecture and regulation of BCL10-MALT1 filaments.
Nat Commun
; 9(1): 4041, 2018 10 02.
Article
em En
| MEDLINE
| ID: mdl-30279415
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteína de Translocação 1 do Linfoma de Tecido Linfoide Associado à Mucosa
/
Proteína 10 de Linfoma CCL de Células B
Idioma:
En
Revista:
Nat Commun
Ano de publicação:
2018
Tipo de documento:
Article