6N1I

Cryo-EM structure of NLRC4-CARD filament

「6DRP」から置き換えられました

6N1I の概要

• エントリーDOI: 10.2210/pdb6n1i/pdb
• EMDBエントリー: 8902 8903
• 分子名称: NLR family CARD domain-containing protein 4 (1 entity in total)
• 機能のキーワード: inflammasome, filament, immunity, signaling protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 16
• 化学式量合計: 159802.74

構造登録者

Li, Y.,Fu, T.,Wu, H. (登録日: 2018-11-08, 公開日: 2018-12-05, 最終更新日: 2024-03-13)

主引用文献

Li, Y.,Fu, T.M.,Lu, A.,Witt, K.,Ruan, J.,Shen, C.,Wu, H.
Cryo-EM structures of ASC and NLRC4 CARD filaments reveal a unified mechanism of nucleation and activation of caspase-1.
Proc. Natl. Acad. Sci. U.S.A., 115:10845-10852, 2018

PubMed Abstract: Canonical inflammasomes are cytosolic supramolecular complexes that activate caspase-1 upon sensing extrinsic microbial invasions and intrinsic sterile stress signals. During inflammasome assembly, adaptor proteins ASC and NLRC4 recruit caspase-1 through homotypic caspase recruitment domain (CARD) interactions, leading to caspase-1 dimerization and activation. Activated caspase-1 processes proinflammatory cytokines and Gasdermin D to induce cytokine maturation and pyroptotic cell death. Here, we present cryo-electron microscopy (cryo-EM) structures of NLRC4 CARD and ASC CARD filaments mediated by conserved three types of asymmetric interactions (types I, II, and III). We find that the CARDs of these two adaptor proteins share a similar assembly pattern, which matches that of the caspase-1 CARD filament whose structure we defined previously. These data indicate a unified mechanism for downstream caspase-1 recruitment through CARD-CARD interactions by both adaptors. Using structure modeling, we further show that full-length NLRC4 assembles via two separate symmetries at its CARD and its nucleotide-binding domain (NBD), respectively.

PubMed: 30279182
DOI: 10.1073/pnas.1810524115

実験手法

ELECTRON MICROSCOPY (3.58 Å)