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Related Experiment Video

Updated: Feb 10, 2026

Engineering a Bilayered Hydrogel to Control ASC Differentiation
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Functional and structural characterization of zebrafish ASC.

Yajuan Li1, Yi Huang1, Xiaocong Cao1

  • 1Laboratory of Structural Immunology, CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, China.

The FEBS Journal
|May 24, 2018
PubMed
Summary

Zebrafish ASC adaptor protein is crucial for inflammasome activation, forming speck and filament structures. Its PYD and CARD domains reveal conserved and unique interactions with fish caspase-1, differing from mammalian pathways.

Keywords:
ASCPYDcaspase-1inflammasomezebrafish

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Area of Science:

  • Immunology
  • Structural Biology
  • Molecular Biology

Background:

  • The zebrafish genome contains homologs for many inflammatory proteins, but fish inflammasome activation mechanisms remain unclear.
  • Apoptosis-associated speck-like protein containing a CARD (ASC) is a key adaptor in mammalian inflammasome formation.

Purpose of the Study:

  • To investigate the role of zebrafish ASC (zASC) in inflammasome activation.
  • To elucidate the structural and functional characteristics of zASC and its interactions with fish caspases.

Main Methods:

  • Overexpression of zASC and its domains in zebrafish.
  • Determination of crystal structures for zASC PYD and CARD domains.
  • Structure-guided mutagenesis and analysis of protein-protein interactions.

Main Results:

  • Overexpressed zASC and its PYD domain form speck and filament structures in zebrafish.
  • Crystal structures revealed functional relevance of the PYD hydrophilic surface.
  • Zebrafish Caspase-1 homolog (Caspy) interacts with zASC via PYD-PYD interactions, distinct from mammalian mechanisms.

Conclusions:

  • Zebrafish ASC is involved in inflammasome activation.
  • The study establishes conserved and unique features of the zASC-dependent inflammasome pathway.
  • Structural insights into zASC provide a basis for understanding fish inflammasome assembly and function.