PUBLICATION
Functional and Structural Characterization of Zebrafish ASC
- Authors
- 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.
- ID
- ZDB-PUB-180526-8
- Date
- 2018
- Source
- The FEBS journal 285(14): 2691-2707 (Journal)
- Registered Authors
- Hu, Bing
- Keywords
- ASC, PYD, caspase-1, inflammasome, zebrafish
- MeSH Terms
-
- Animals
- Gene Expression
- Protein Multimerization
- Protein Interaction Domains and Motifs
- Cytoskeletal Proteins/chemistry*
- Cytoskeletal Proteins/genetics
- Cytoskeletal Proteins/immunology
- Maltose-Binding Proteins/chemistry
- Maltose-Binding Proteins/genetics
- Maltose-Binding Proteins/immunology
- Zebrafish/genetics*
- Zebrafish/immunology
- Inflammasomes/genetics*
- Inflammasomes/immunology
- Protein Conformation, alpha-Helical
- Escherichia coli/genetics
- Escherichia coli/metabolism
- Gills/immunology
- Gills/metabolism
- Amino Acid Sequence
- Sequence Homology, Amino Acid
- Crystallography, X-Ray
- Genetic Vectors/chemistry
- Genetic Vectors/metabolism
- Protein Binding
- Protein Conformation, beta-Strand
- Binding Sites
- Models, Molecular
- Sequence Alignment
- Intestines/immunology
- Zebrafish Proteins/chemistry*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/immunology
- Caspases/chemistry*
- Caspases/genetics
- Caspases/immunology
- Cloning, Molecular
- Hydrophobic and Hydrophilic Interactions
- Recombinant Fusion Proteins/chemistry
- Recombinant Fusion Proteins/genetics
- Recombinant Fusion Proteins/immunology
- PubMed
- 29791979 Full text @ FEBS J.
Citation
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. (2018) Functional and Structural Characterization of Zebrafish ASC. The FEBS journal. 285(14):2691-2707.
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 (MBP). 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. This article is protected by copyright. All rights reserved.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping