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Schlauderer, F.* ; Seeholzer, T. ; Desfosses, A.* ; Gehring, T. ; Strauss, M.* ; Hopfner, K.P.* ; Gutsche, I.* ; Krappmann, D. ; Lammens, K.*

Molecular architecture and regulation of BCL10-MALT1 filaments.

Nat. Commun. 9:4041 (2018)
Verlagsversion Forschungsdaten DOI PMC
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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 angstrom 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-kappa B 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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Nf-kappa-b; T-cell-activation; Lymphoid-tissue Lymphomas; Combined Immunodeficiency; Paracaspase Malt1; Card11 Mutations; Chromosomal Translocation; Electron-microscopy; Abc-dlbcl; Bcl10
Sprache englisch
Veröffentlichungsjahr 2018
HGF-Berichtsjahr 2018
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 9, Heft: 1, Seiten: , Artikelnummer: 4041 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Signaling and Translation (SAT)
POF Topic(s) 30203 - Molecular Targets and Therapies
Forschungsfeld(er) Enabling and Novel Technologies
PSP-Element(e) G-509800-002
DOI 10.1038/s41467-018-06573-8
WOS ID WOS:000446017000009
Scopus ID 85054169338
PubMed ID 30279415
Erfassungsdatum 2018-10-19
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