The inflammasome adapter ASC and truncated constructs containing only its Death Domains self‐assemble into different macrostructures

Abstract

ASC (apoptosis‐associated speck‐like protein containing a CARD) is an adaptor protein that mediates in inflammasome assembly. The inflammasome is a multiprotein complex that triggers the inflammatory response. Multiple copies of a sensor protein, procaspase‐1 and ASC acting as a molecular bridge between them, self‐associate and oligomerize to form the inflammasome particle, a micrometer‐size filamentous ring in the cell cytosol. Thus, ASC self‐assembly properties and interacting capabilities via its two Death Domains (PYD and CARD) are critical for inflammasome formation. Our Transmission Electron Microscopy (TEM) studies show that full length ASC, and the truncated constructs ASCPYD and ASCCARD, form macrostructures with significantly different characteristics. In addition, we have analyzed in detail the ASCCARD–ASCCARD interaction by solution NMR and TEM, which is of particular relevance due to the current lack of information. Our analysis includes CARD mutants designed based on the NMR data.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.