title: Structural insights into the assembly of CARMA1 and BCL10.
abstract: The CBM complex (CARMA1, BCL10 and MALT1) plays a crucial role in B and T lymphocyte activation. CARMA1 serves as a scaffold for BCL10, MALT1 and other effector proteins and regulates various signaling pathways related to the immune response. The assembly of CARMA1 and BCL10 is mediated through a CARD-CARD interaction. Here, we report the crystal structure of the CARD domain of CARMA1 at a resolution of 1.75 Å. The structure consists of six helices, as previously determined for CARD domains. Structural and computational analysis identified the binding interface between CARMA1-CARD and BCL10-CARD, which consists of a basic patch in CARMA1 and an acidic patch in BCL10. Site-directed mutagenesis, co-immunoprecipitation and an NF-κB activation assay confirmed that the interface is necessary for association and downstream signaling. Our studies provide molecular insight into the assembly of CARMA1 and BCL10.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China.
authors.forename: Siwei
authors.initials: S
authors.lastname: Li
authors.forename: Xue
authors.initials: X
authors.lastname: Yang
authors.forename: Juan
authors.initials: J
authors.lastname: Shao
authors.forename: Yuequan
authors.initials: Y
authors.lastname: Shen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000378:metabolism*; D000595:Amino Acid Sequence; D000074018:B-Cell CLL-Lymphoma 10 Protein; D001665:Binding Sites; D053468:CARD Signaling Adaptor Proteins / Q000737:chemistry* / Q000378:metabolism*; D018360:Crystallography, X-Ray; D057809:HEK293 Cells; D006801:Humans; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D013499:Surface Properties
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000074018:B-Cell CLL-Lymphoma 10 Protein; C488088:Bcl10 protein, mouse; D053468:CARD Signaling Adaptor Proteins; C496467:Card11 protein, mouse