2mb9
From Proteopedia
Human Bcl10 CARD
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 PubMedThe 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. See AlsoReferences
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Categories: Human | Large Structures | Bracken, C | Wu, H | Zheng, C | Apoptosis | Death domain | Signaling protein
