6N2P

Helical assembly of the CARD9 CARD

6N2P の概要

• エントリーDOI: 10.2210/pdb6n2p/pdb
• 関連するPDBエントリー: 6N2M
• EMDBエントリー: 9332
• 分子名称: Caspase recruitment domain-containing protein 9 (1 entity in total)
• 機能のキーワード: card, filament, helical assembly, death domain, innate immunity, signaling protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 173518.73

構造登録者

Holliday, M.J.,Rohou, A.,Arthur, C.P.,Dueber, E.C.,Fairbrother, W.J. (登録日: 2018-11-13, 公開日: 2019-07-03, 最終更新日: 2024-03-20)

主引用文献

Holliday, M.J.,Witt, A.,Rodriguez Gama, A.,Walters, B.T.,Arthur, C.P.,Halfmann, R.,Rohou, A.,Dueber, E.C.,Fairbrother, W.J.
Structures of autoinhibited and polymerized forms of CARD9 reveal mechanisms of CARD9 and CARD11 activation.
Nat Commun, 10:3070-3070, 2019

PubMed Abstract: CARD9 and CARD11 drive immune cell activation by nucleating Bcl10 polymerization, but are held in an autoinhibited state prior to stimulation. Here, we elucidate the structural basis for this autoinhibition by determining the structure of a region of CARD9 that includes an extensive interface between its caspase recruitment domain (CARD) and coiled-coil domain. We demonstrate, for both CARD9 and CARD11, that disruption of this interface leads to hyperactivation in cells and to the formation of Bcl10-templating filaments in vitro, illuminating the mechanism of action of numerous oncogenic mutations of CARD11. These structural insights enable us to characterize two similar, yet distinct, mechanisms by which autoinhibition is relieved in the course of canonical CARD9 or CARD11 activation. We also dissect the molecular determinants of helical template assembly by solving the structure of the CARD9 filament. Taken together, these findings delineate the structural mechanisms of inhibition and activation within this protein family.

PubMed: 31296852
DOI: 10.1038/s41467-019-10953-z

実験手法

ELECTRON MICROSCOPY (4 Å)