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TitleAssembly mechanism of the CARMA1-BCL10-MALT1-TRAF6 signalosome.
Journal, issue, pagesProc Natl Acad Sci U S A, Vol. 115, Issue 7, Page 1499-1504, Year 2018
Publish dateFeb 13, 2018
AuthorsLiron David / Yang Li / Jun Ma / Ethan Garner / Xinzheng Zhang / Hao Wu /
PubMed AbstractThe CARMA1-BCL10-MALT1 (CBM) signalosome is a central mediator of T cell receptor and B cell receptor-induced NF-κB signaling that regulates multiple lymphocyte functions. While caspase-recruitment ...The CARMA1-BCL10-MALT1 (CBM) signalosome is a central mediator of T cell receptor and B cell receptor-induced NF-κB signaling that regulates multiple lymphocyte functions. While caspase-recruitment domain (CARD) membrane-associated guanylate kinase (MAGUK) protein 1 (CARMA1) nucleates B cell lymphoma 10 (BCL10) filament formation through interactions between CARDs, mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is a paracaspase with structural similarity to caspases, which recruits TNF receptor-associated factor 6 (TRAF6) for K63-linked polyubiquitination. Here we present cryo-electron microscopy (cryo-EM) structure of the BCL10 CARD filament at 4.0-Å resolution. The structure redefines CARD-CARD interactions compared with the previous EM structure determined from a negatively stained sample. Surprisingly, time-lapse confocal imaging shows that BCL10 polymerizes in a unidirectional manner. CARMA1, the BCL10 nucleator, serves as a hub for formation of star-shaped filamentous networks of BCL10 and significantly decreases the lag period of BCL10 polymerization. Cooperative MALT1 interaction with BCL10 filaments observed under EM suggests immediate dimerization of MALT1 in the BCL10 filamentous scaffold. In addition, TRAF6 cooperatively decorates CBM filaments to form higher-order assemblies, likely resulting in all-or-none activation of the downstream pathway. Collectively, these data reveal biophysical mechanisms in the assembly of the CARMA1-BCL10-MALT1-TRAF6 complex for signal transduction.
External linksProc Natl Acad Sci U S A / PubMed:29382759 / PubMed Central
MethodsEM (helical sym.)
Resolution4.0 Å
Structure data

EMDB-7314, PDB-6bze:
Cryo-EM structure of BCL10 CARD filament
Method: EM (helical sym.) / Resolution: 4.0 Å

Source
  • homo sapiens (human)
KeywordsSIGNALING PROTEIN / CARD / filament / signalosome / helical reconstruction

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