5FNA

Cryo-EM reconstruction of caspase-1 CARD

5FNA の概要

• エントリーDOI: 10.2210/pdb5fna/pdb
• EMDBエントリー: 3241
• 分子名称: Caspase-1 (1 entity in total)
• 機能のキーワード: hydrolase, card, inflammasome, filament, signalosome, helical reconstruction, death domain
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 76721.37

構造登録者

Li, Y.,Lu, A.,Schmidt, F.I.,Yin, Q.,Chen, S.,Fu, T.M.,Tong, A.B.,Ploegh, H.L.,Mao, Y.,Wu, H. (登録日: 2015-11-11, 公開日: 2016-03-30, 最終更新日: 2024-05-08)

主引用文献

Li, Y.,Lu, A.,Schmidt, F.I.,Yin, Q.,Chen, S.,Fu, T.M.,Tong, A.B.,Ploegh, H.L.,Mao, Y.,Wu, H.
Molecular Basis of Caspase-1 Polymerization and its Inhibition by a Novel Capping Mechanism
Nat.Struct.Mol.Biol., 23:416-, 2016

PubMed Abstract: Inflammasomes are cytosolic caspase-1-activation complexes that sense intrinsic and extrinsic danger signals, and trigger inflammatory responses and pyroptotic cell death. Homotypic interactions among Pyrin domains and caspase recruitment domains (CARDs) in inflammasome-complex components mediate oligomerization into filamentous assemblies. Several cytosolic proteins consisting of only interaction domains exert inhibitory effects on inflammasome assembly. In this study, we determined the structure of the human caspase-1 CARD domain (caspase-1(CARD)) filament by cryo-electron microscopy and investigated the biophysical properties of two caspase-1-like CARD-only proteins: human inhibitor of CARD (INCA or CARD17) and ICEBERG (CARD18). Our results reveal that INCA caps caspase-1 filaments, thereby exerting potent inhibition with low-nanomolar Ki on caspase-1(CARD) polymerization in vitro and inflammasome activation in cells. Whereas caspase-1(CARD) uses six complementary surfaces of three types for filament assembly, INCA is defective in two of the six interfaces and thus terminates the caspase-1 filament.

PubMed: 27043298
DOI: 10.1038/NSMB.3199

実験手法

ELECTRON MICROSCOPY (4.8 Å)