5GPQ

Crystal Structure of zebrafish ASC CARD Domain

5GPQ の概要

• エントリーDOI: 10.2210/pdb5gpq/pdb
• 関連するPDBエントリー: 5GPP
• 関連するBIRD辞書のPRD_ID: PRD_900001
• 分子名称: Maltose-binding periplasmic protein,Apoptosis-associated speck-like protein containing a CARD, alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose, CITRIC ACID, ... (4 entities in total)
• 機能のキーワード: death fold, innate immune signaling, immune system
• 由来する生物種: Escherichia coli O157:H7; 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 52188.94

構造登録者

Jin, T.,Li, Y. (登録日: 2016-08-04, 公開日: 2017-08-09, 最終更新日: 2024-03-20)

主引用文献

Li, Y.,Huang, Y.,Cao, X.,Yin, X.,Jin, X.,Liu, S.,Jiang, J.,Jiang, W.,Xiao, T.S.,Zhou, R.,Cai, G.,Hu, B.,Jin, T.
Functional and structural characterization of zebrafish ASC.
FEBS J., 285:2691-2707, 2018

PubMed Abstract: The zebrafish genome encodes homologs for most of the proteins involved in inflammatory pathways; however, the molecular components and activation mechanisms of fish inflammasomes are largely unknown. ASC [apoptosis-associated speck-like protein containing a caspase-recruitment domain (CARD)] is the only adaptor involved in the formation of multiple types of inflammasomes. Here, we demonstrate that zASC is also involved in inflammasome activation in zebrafish. When overexpressed in vitro and in vivo in zebrafish, both the zASC and zASC pyrin domain (PYD) proteins form speck and filament structures. Importantly, the crystal structures of the N-terminal PYD and C-terminal CARD of zebrafish ASC were determined independently as two separate entities fused to maltose-binding protein. Structure-guided mutagenesis revealed the functional relevance of the PYD hydrophilic surface found in the crystal lattice. Finally, the fish caspase-1 homolog Caspy, but not the caspase-4/11 homolog Caspy2, interacts with zASC through homotypic PYD-PYD interactions, which differ from those in mammals. These observations establish the conserved and unique structural/functional features of the zASC-dependent inflammasome pathway.

PubMed: 29791979
DOI: 10.1111/febs.14514

実験手法

X-RAY DIFFRACTION (2.1 Å)