Structural highlights
Disease
BCL10_HUMAN A chromosomal aberration involving BCL10 is recurrent in low-grade mucosa-associated lymphoid tissue (MALT lymphoma). Translocation t(1;14)(p22;q32). Although the BCL10/IgH translocation leaves the coding region of BCL10 intact, frequent BCL10 mutations could be attributed to the Ig somatic hypermutation mechanism resulting in nucleotide transitions. Defects in BCL10 are involved in various types of cancer. The gene represented in this entry may be involved in disease pathogenesis.
Function
BCL10_HUMAN Promotes apoptosis, pro-caspase-9 maturation and activation of NF-kappa-B via NIK and IKK. May be an adapter protein between upstream TNFR1-TRADD-RIP complex and the downstream NIK-IKK-IKAP complex. Is a substrate for MALT1.[1]
Publication Abstract from PubMed
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 A 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-kappaB 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.
Molecular architecture and regulation of BCL10-MALT1 filaments.,Schlauderer F, Seeholzer T, Desfosses A, Gehring T, Strauss M, Hopfner KP, Gutsche I, Krappmann D, Lammens K Nat Commun. 2018 Oct 2;9(1):4041. doi: 10.1038/s41467-018-06573-8. PMID:30279415[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Rebeaud F, Hailfinger S, Posevitz-Fejfar A, Tapernoux M, Moser R, Rueda D, Gaide O, Guzzardi M, Iancu EM, Rufer N, Fasel N, Thome M. The proteolytic activity of the paracaspase MALT1 is key in T cell activation. Nat Immunol. 2008 Mar;9(3):272-81. doi: 10.1038/ni1568. Epub 2008 Feb 10. PMID:18264101 doi:10.1038/ni1568
- ↑ Schlauderer F, Seeholzer T, Desfosses A, Gehring T, Strauss M, Hopfner KP, Gutsche I, Krappmann D, Lammens K. Molecular architecture and regulation of BCL10-MALT1 filaments. Nat Commun. 2018 Oct 2;9(1):4041. doi: 10.1038/s41467-018-06573-8. PMID:30279415 doi:http://dx.doi.org/10.1038/s41467-018-06573-8
