6BZE

Cryo-EM structure of BCL10 CARD filament

6BZE の概要

• エントリーDOI: 10.2210/pdb6bze/pdb
• EMDBエントリー: 7314
• 分子名称: B-cell lymphoma/leukemia 10 (1 entity in total)
• 機能のキーワード: card, filament, signalosome, helical reconstruction, signaling protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 100916.53

構造登録者

David, L.,Li, Y.,Ma, J.,Garner, E.,Zhang, X.,Wu, H. (登録日: 2017-12-23, 公開日: 2018-02-14, 最終更新日: 2024-03-13)

主引用文献

David, L.,Li, Y.,Ma, J.,Garner, E.,Zhang, X.,Wu, H.
Assembly mechanism of the CARMA1-BCL10-MALT1-TRAF6 signalosome.
Proc. Natl. Acad. Sci. U.S.A., 115:1499-1504, 2018

PubMed Abstract: 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.

PubMed: 29382759
DOI: 10.1073/pnas.1721967115

実験手法

ELECTRON MICROSCOPY (4 Å)