7LFH

Cryo-EM structure of NLRP3 double-ring cage, 6-fold (12-mer)

7LFH の概要

• エントリーDOI: 10.2210/pdb7lfh/pdb
• EMDBエントリー: 23302 23303 23304 23305
• 分子名称: NACHT, LRR and PYD domains-containing protein 3 (1 entity in total)
• 機能のキーワード: nlrp3, nek7, nucleotid-binding, atp-binding, inflammasome, immunity, innate immunity, nacht, lrr, pyd, immune system
• 由来する生物種: Mus musculus (house mouse)
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 1425626.63

構造登録者

Andreeva, L.,Rawson, S.,Wu, H. (登録日: 2021-01-17, 公開日: 2021-12-15, 最終更新日: 2024-05-29)

主引用文献

Andreeva, L.,David, L.,Rawson, S.,Shen, C.,Pasricha, T.,Pelegrin, P.,Wu, H.
NLRP3 cages revealed by full-length mouse NLRP3 structure control pathway activation.
Cell, 184:6299-, 2021

PubMed Abstract: The NACHT-, leucine-rich-repeat- (LRR), and pyrin domain-containing protein 3 (NLRP3) is emerging to be a critical intracellular inflammasome sensor of membrane integrity and a highly important clinical target against chronic inflammation. Here, we report that an endogenous, stimulus-responsive form of full-length mouse NLRP3 is a 12- to 16-mer double-ring cage held together by LRR-LRR interactions with the pyrin domains shielded within the assembly to avoid premature activation. Surprisingly, this NLRP3 form is predominantly membrane localized, which is consistent with previously noted localization of NLRP3 at various membrane organelles. Structure-guided mutagenesis reveals that trans-Golgi network dispersion into vesicles, an early event observed for many NLRP3-activating stimuli, requires the double-ring cages of NLRP3. Double-ring-defective NLRP3 mutants abolish inflammasome punctum formation, caspase-1 processing, and cell death. Thus, our data uncover a physiological NLRP3 oligomer on the membrane that is poised to sense diverse signals to induce inflammasome activation.

PubMed: 34861190
DOI: 10.1016/j.cell.2021.11.011

実験手法

ELECTRON MICROSCOPY (4.2 Å)