Proteomics

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Identification of gasderminD interacting proteins by mass spectrometry


ABSTRACT: Gasdermin D (GSDMD)-mediated macrophage pyroptosis plays a critical role in inflammation and host defense. Plasma membrane perforation elicited by caspase-cleaved GSDMD N-terminal domain (GSDMD-NT) triggers membrane rupture and subsequent pyroptotic cell death, resulting in release of pro-inflammatory IL-1β and IL-18. Here, using a proteomics approach, we identified fatty acid synthase (FASN) as a GSDMD-binding partner and demonstrated that post-translational palmitoylation of GSDMD at Cys191/Cys192 (human/mouse) led to membrane translocation of GSDMD-NT but not full-length GSDMD. Collectively, we establish GSDMD-NT palmitoylation as a key regulatory mechanism modulating immune activity in infectious and inflammatory diseases.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

SUBMITTER: Arumugam Balasubramanian  

LAB HEAD: Hongbo R Luo

PROVIDER: PXD039133 | Pride | 2025-05-06

REPOSITORIES: Pride

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Publications


Plasma membrane perforation elicited by caspase cleavage of the gasdermin D (GSDMD) N-terminal domain (GSDMD-NT) triggers pyroptosis. The mechanisms underlying GSDMD membrane translocation and pore formation are not fully understood. Here, using a proteomic approach, we identified fatty acid synthase (FASN) as a GSDMD-binding partner. S-palmitoylation of GSDMD at Cys<sup>191</sup>/Cys<sup>192</sup> (human/mouse), catalyzed by palmitoyl acyltransferases ZDHHC5 and ZDHHC9 and facilitated by reacti  ...[more]

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