PLoS One. 2012;7(8):e42775. Epub 2012 Aug 3.

Structural insights into the assembly of CARMA1 and BCL10.External

Li, S., Yang, X., Shao, J., Shen, Y.,
--- - State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China.
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 A. 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-kappaB 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.
PMID: 22880103External
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vivo interaction
  Endogenous
expression
Overexpression DD1 DD2 Reference
Family DD1 DD2 Method Species Region Species Region
CARD Bcl-10 Link CARMA1 Co-immunoprecipitation HEK293 Mouse 1-121 Mouse 1-155 22880103
(Link: click this icon to show interactions only between the two corresponding DDs)
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
Characterization
  Stoichiometry Affinity Protein-Protein interface Reference
Family DD1 DD2 Method Mutation Complex structure
CARD Bcl-10 Link CARMA1 Co-immunoprecipitation R35A (CARMA1) E53A, E54A (Bcl-10) 22880103
(Link: click this icon to show interactions only between the two corresponding DDs)