Dynamic <i>S</i>-acylation of GSDMA regulates pyroptosis.

ABSTRACT: GSDMA, the primary member of the gasdermin family found in the skin, is critical for pathogen-induced pyroptosis during infection. Recent studies revealed that another gasdermin, GSDMD, undergoes palmitoylation during pyroptosis. However, whether and how the other gasdermin members undergo lipid modification remains poorly understood. Here, we demonstrate that GSDMA is S-acylated at the conserved cysteine residues in its N-terminal domain. We show that S-acylation of GSDMA promotes pyroptosis by facilitating its membrane anchoring and protein oligomerization, a mechanism distinct from the palmitoylation of GSDMD at the N-terminal C191 residue. Additionally, we present evidence that recombinant proteins of GSDMA and GSDMD can undergo S-acylation in vitro via dire

SUBMITTER: Tao Z 

PROVIDER: S-EPMC12633010 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature