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Detection of Inflammasome Activation and Pyroptotic Cell Death in Murine Bone Marrow-derived Macrophages
Published on: May 21, 2018
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Structure, interactions and self-assembly of ASC-dependent inflammasomes
1Department of Bioengineering. School of Engineering. University of California, Merced, 5200 North Lake Road, Merced, CA, 95343, USA.
Archives of Biochemistry and Biophysics
|June 2, 2019
Summary
The inflammasome, crucial for innate immunity, assembles via the ASC protein. Understanding ASC's biophysical properties and interactions is key to fighting autoimmune disorders linked to inflammasome dysfunction.
Area of Science:
- Immunology
- Structural Biology
- Biophysics
Background:
- The inflammasome is a protein complex critical for innate immunity, mediating inflammatory responses to infection and tissue damage.
- Dysregulation of inflammasome assembly is implicated in various autoimmune disorders.
- The apoptosis-associated speck-like protein containing a CARD (ASC) is a key adapter protein in inflammasome formation.
Purpose of the Study:
- To review the biophysical aspects of inflammasome assembly, focusing on the role of ASC.
- To elucidate the relationship between ASC's structure, dynamics, and function in inflammasome formation.
- To provide insights into ASC interacting surfaces and macrostructure formation for a directional model of inflammasome assembly.
Main Methods:
- Nuclear Magnetic Resonance (NMR) spectroscopy to identify ASC interacting surfaces at the amino acid level.
- Transmission Electron Microscopy (TEM) to study macrostructures formed by full-length ASC and its Death Domains.
- Analysis of the three-dimensional solution structure and interdomain dynamics of ASC.
Main Results:
- Detailed characterization of ASC's three-dimensional structure and interdomain dynamics.
- Identification of specific amino acid residues involved in ASC interactions.
- Comparison of macrostructures formed by full-length ASC and its domains, supporting a directional model for inflammasome assembly.
Conclusions:
- Understanding the biophysical properties of ASC is essential for comprehending inflammasome assembly.
- ASC's structure and dynamics directly influence its function in mediating inflammatory responses.
- These findings contribute to developing strategies against autoimmune diseases driven by inflammasome dysregulation.
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