Structural insights into the assembly of CARMA1 and BCL10

PLoS One. 2012;7(8):e42775. doi: 10.1371/journal.pone.0042775. Epub 2012 Aug 3.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry*
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Amino Acid Sequence
  • B-Cell CLL-Lymphoma 10 Protein
  • Binding Sites
  • CARD Signaling Adaptor Proteins / chemistry*
  • CARD Signaling Adaptor Proteins / metabolism*
  • Crystallography, X-Ray
  • HEK293 Cells
  • Humans
  • Molecular Docking Simulation
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • Surface Properties

Substances

  • Adaptor Proteins, Signal Transducing
  • B-Cell CLL-Lymphoma 10 Protein
  • Bcl10 protein, mouse
  • CARD Signaling Adaptor Proteins
  • Card11 protein, mouse

Grants and funding

This work was funded by the 973 Program (grants 2012CB917201 and 2009CB825504), NSFC (grant 31170684) and the Fundamental Research Funds for the Central Universities (grant 65020241).The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.