2MB9

Human Bcl10 CARD

2MB9 の概要

• エントリーDOI: 10.2210/pdb2mb9/pdb
• NMR情報: BMRB: 19392
• 分子名称: B-cell lymphoma/leukemia 10 (1 entity in total)
• 機能のキーワード: death domain, apoptosis, signaling protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm, perinuclear region: O95999
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 13852.98

構造登録者

Zheng, C.,Bracken, C.,Wu, H. (登録日: 2013-07-26, 公開日: 2013-10-16, 最終更新日: 2024-05-15)

主引用文献

Qiao, Q.,Yang, C.,Zheng, C.,Fontan, L.,David, L.,Yu, X.,Bracken, C.,Rosen, M.,Melnick, A.,Egelman, E.H.,Wu, H.
Structural Architecture of the CARMA1/Bcl10/MALT1 Signalosome: Nucleation-Induced Filamentous Assembly.
Mol.Cell, 51:766-779, 2013

PubMed Abstract: The CARMA1/Bcl10/MALT1 (CBM) signalosome mediates antigen receptor-induced NF-κB signaling to regulate multiple lymphocyte functions. While CARMA1 and Bcl10 contain caspase recruitment domains (CARDs), MALT1 is a paracaspase with structural similarity to caspases. Here we show that the reconstituted CBM signalosome is a helical filamentous assembly in which substoichiometric CARMA1 nucleates Bcl10 filaments. Bcl10 filament formation is a highly cooperative process whose threshold is sensitized by oligomerized CARMA1 upon receptor activation. In cells, both cotransfected CARMA1/Bcl10 complex and the endogenous CBM signalosome are filamentous morphologically. Combining crystallography, nuclear magnetic resonance, and electron microscopy, we reveal the structure of the Bcl10 CARD filament and the mode of interaction between CARMA1 and Bcl10. Structure-guided mutagenesis confirmed the observed interfaces in Bcl10 filament assembly and MALT1 activation in vitro and NF-κB activation in cells. These data support a paradigm of nucleation-induced signal transduction with threshold response due to cooperativity and signal amplification by polymerization.

PubMed: 24074955
DOI: 10.1016/j.molcel.2013.08.032

実験手法

SOLUTION NMR