4lwd
From Proteopedia
Human CARMA1 CARD domain
Structural highlights
DiseaseCAR11_HUMAN Persistent polyclonal B-cell lymphocytosis. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. FunctionCAR11_HUMAN Involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation. Its binding to DPP4 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner. Activates NF-kappa-B via BCL10 and IKK. Stimulates the phosphorylation of BCL10. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||
