4.6 Article

Structural Insights into the Assembly of CARMA1 and BCL10

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PLOS ONE
卷 7, 期 8, 页码 -

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PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0042775

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资金

  1. 973 Program [2012CB917201, 2009CB825504]
  2. NSFC [31170684]
  3. Fundamental Research Funds for the Central Universities [65020241]

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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 angstrom. 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-kappa B 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.

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