4LWD

Human CARMA1 CARD domain

Summary for 4LWD

• Entry DOI: 10.2210/pdb4lwd/pdb
• Descriptor: Caspase recruitment domain-containing protein 11, SULFATE ION, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: death domain, bcl10, signaling protein
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: Q9BXL7
• Total number of polymer chains: 1
• Total formula weight: 11698.49

Authors

Zheng, C.,Wu, H. (deposition date: 2013-07-26, release date: 2013-10-16, Last modification date: 2024-02-28)

Primary citation

Qiao, Q.,Yang, C.,Zheng, C.,Fontan, L.,David, L.,Yu, X.,Bracken, C.,Rosen, M.,Melnick, A.,Egelman, E.H.,Wu, H.
Structural Architecture of the CARMA1/Bcl10/MALT1 Signalosome: Nucleation-Induced Filamentous Assembly.
Mol.Cell, 51:766-779, 2013

PubMed Abstract: The CARMA1/Bcl10/MALT1 (CBM) signalosome mediates antigen receptor-induced NF-κB 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-κB activation in cells. These data support a paradigm of nucleation-induced signal transduction with threshold response due to cooperativity and signal amplification by polymerization.

PubMed: 24074955
DOI: 10.1016/j.molcel.2013.08.032

Experimental method

X-RAY DIFFRACTION (1.792 Å)