6GGS

Structure of RIP2 CARD filament

6GGS の概要

• エントリーDOI: 10.2210/pdb6ggs/pdb
• EMDBエントリー: 4399
• 分子名称: Receptor-interacting serine/threonine-protein kinase 2 (1 entity in total)
• 機能のキーワード: card, rip2, filament, helical, transferase
• 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: 125864.78

構造登録者

Pellegrini, E.,Cusack, S.,Desfosses, A.,Schoehn, G.,Malet, H.,Gutsche, I.,Sachse, C.,Hons, M. (登録日: 2018-05-03, 公開日: 2018-10-17, 最終更新日: 2024-05-15)

主引用文献

Pellegrini, E.,Desfosses, A.,Wallmann, A.,Schulze, W.M.,Rehbein, K.,Mas, P.,Signor, L.,Gaudon, S.,Zenkeviciute, G.,Hons, M.,Malet, H.,Gutsche, I.,Sachse, C.,Schoehn, G.,Oschkinat, H.,Cusack, S.
RIP2 filament formation is required for NOD2 dependent NF-kappa B signalling.
Nat Commun, 9:4043-4043, 2018

PubMed Abstract: Activation of the innate immune pattern recognition receptor NOD2 by the bacterial muramyl-dipeptide peptidoglycan fragment triggers recruitment of the downstream adaptor kinase RIP2, eventually leading to NF-κB activation and proinflammatory cytokine production. Here we show that full-length RIP2 can form long filaments mediated by its caspase recruitment domain (CARD), in common with other innate immune adaptor proteins. We further show that the NOD2 tandem CARDs bind to one end of the RIP2 CARD filament, suggesting a mechanism for polar filament nucleation by activated NOD2. We combine X-ray crystallography, solid-state NMR and high-resolution cryo-electron microscopy to determine the atomic structure of the helical RIP2 CARD filament, which reveals the intermolecular interactions that stabilize the assembly. Using structure-guided mutagenesis, we demonstrate the importance of RIP2 polymerization for the activation of NF-κB signalling by NOD2. Our results could be of use to develop new pharmacological strategies to treat inflammatory diseases characterised by aberrant NOD2 signalling.

PubMed: 30279485
DOI: 10.1038/s41467-018-06451-3

実験手法

ELECTRON MICROSCOPY (3.94 Å)