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Molecular architecture and regulation of BCL10-MALT1 filaments

Author

Listed:
  • Florian Schlauderer

    (Ludwig-Maximilians University)

  • Thomas Seeholzer

    (Institute of Molecular Toxicology and Pharmacology, Helmholtz-Zentrum München - German Research Center for Environmental Health)

  • Ambroise Desfosses

    (University Grenoble Alpes, CNRS, CEA, Institut de Biologie Structurale IBS)

  • Torben Gehring

    (Institute of Molecular Toxicology and Pharmacology, Helmholtz-Zentrum München - German Research Center for Environmental Health)

  • Mike Strauss

    (McGill University)

  • Karl-Peter Hopfner

    (Ludwig-Maximilians University)

  • Irina Gutsche

    (University Grenoble Alpes, CNRS, CEA, Institut de Biologie Structurale IBS)

  • Daniel Krappmann

    (Institute of Molecular Toxicology and Pharmacology, Helmholtz-Zentrum München - German Research Center for Environmental Health)

  • Katja Lammens

    (Ludwig-Maximilians University)

Abstract

The CARD11-BCL10-MALT1 (CBM) complex triggers the adaptive immune response in lymphocytes and lymphoma cells. CARD11/CARMA1 acts as a molecular seed inducing BCL10 filaments, but the integration of MALT1 and the assembly of a functional CBM complex has remained elusive. Using cryo-EM we solved the helical structure of the BCL10-MALT1 filament. The structural model of the filament core solved at 4.9 Å resolution identified the interface between the N-terminal MALT1 DD and the BCL10 caspase recruitment domain. The C-terminal MALT1 Ig and paracaspase domains protrude from this core to orchestrate binding of mediators and substrates at the filament periphery. Mutagenesis studies support the importance of the identified BCL10-MALT1 interface for CBM complex assembly, MALT1 protease activation and NF-κB signaling in Jurkat and primary CD4 T-cells. Collectively, we present a model for the assembly and architecture of the CBM signaling complex and how it functions as a signaling hub in T-lymphocytes.

Suggested Citation

  • Florian Schlauderer & Thomas Seeholzer & Ambroise Desfosses & Torben Gehring & Mike Strauss & Karl-Peter Hopfner & Irina Gutsche & Daniel Krappmann & Katja Lammens, 2018. "Molecular architecture and regulation of BCL10-MALT1 filaments," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06573-8
    DOI: 10.1038/s41467-018-06573-8
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    Cited by:

    1. Leonard Campanello & Maria K Traver & Hari Shroff & Brian C Schaefer & Wolfgang Losert, 2021. "Signaling through polymerization and degradation: Analysis and simulations of T cell activation mediated by Bcl10," PLOS Computational Biology, Public Library of Science, vol. 17(5), pages 1-24, May.

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