2mb9

From Proteopedia

Human Bcl10 CARD

PDB ID 2mb9

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Structural highlights

2mb9 is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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 CARMA1/Bcl10/MALT1 (CBM) signalosome mediates antigen receptor-induced NF-kappaB signaling to regulate multiple lymphocyte functions. While CARMA1 and Bcl10 contain caspase recruitment domains (CARDs), MALT1 is a paracaspase with structural similarity to caspases. Here we show that the reconstituted CBM signalosome is a helical filamentous assembly in which substoichiometric CARMA1 nucleates Bcl10 filaments. Bcl10 filament formation is a highly cooperative process whose threshold is sensitized by oligomerized CARMA1 upon receptor activation. In cells, both cotransfected CARMA1/Bcl10 complex and the endogenous CBM signalosome are filamentous morphologically. Combining crystallography, nuclear magnetic resonance, and electron microscopy, we reveal the structure of the Bcl10 CARD filament and the mode of interaction between CARMA1 and Bcl10. Structure-guided mutagenesis confirmed the observed interfaces in Bcl10 filament assembly and MALT1 activation in vitro and NF-kappaB activation in cells. These data support a paradigm of nucleation-induced signal transduction with threshold response due to cooperativity and signal amplification by polymerization.

Structural Architecture of the CARMA1/Bcl10/MALT1 Signalosome: Nucleation-Induced Filamentous Assembly.,Qiao Q, Yang C, Zheng C, Fontan L, David L, Yu X, Bracken C, Rosen M, Melnick A, Egelman EH, Wu H Mol Cell. 2013 Sep 26;51(6):766-79. doi: 10.1016/j.molcel.2013.08.032. PMID:24074955^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ Qiao Q, Yang C, Zheng C, Fontan L, David L, Yu X, Bracken C, Rosen M, Melnick A, Egelman EH, Wu H. Structural Architecture of the CARMA1/Bcl10/MALT1 Signalosome: Nucleation-Induced Filamentous Assembly. Mol Cell. 2013 Sep 26;51(6):766-79. doi: 10.1016/j.molcel.2013.08.032. PMID:24074955 doi:http://dx.doi.org/10.1016/j.molcel.2013.08.032