GSDMD
a member of the gasdermin family of proteins that play important roles during infection, inflammation and cell death. The N-terminal fragment of gasdermin-D (GSDMD) is a critical effector of pyroptosis, a lytic type of cell death triggered by inflammasomes, multiprotein complexes assembled in response to pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs) that result in the activation of caspase-1 and subsequent cleavage of pro-inflammatory cytokines IL-1_ and IL-18. Is cleaved by the inflammatory caspases 1, 4, 5 or 11 in response to canonical, as well as non-canonical (such as cytosolic LPS), inflammasome activators. After cleavage, its N-terminal fragment (GSDMD-N) moves to the plasma membrane (PM), where it oligomerizes, forming pores possibly allowing the release of mature IL1B and triggering pyroptosis. GSDMD-N strongly binds to inner leaflet lipids, including monophosphorylated phosphatidylinositols, such as phosphatidylinositol 4-phosphate, bisphosphorylated phosphatidylinositols, such as phosphatidylinositol (4,5)-bisphosphate, as well as phosphatidylinositol (3,4,5)-bisphosphate, and more weakly to phosphatidic acid and phosphatidylserine. GSDMD-N exhibits bactericidal activity. When released from pyroptotic cells into the extracellular milieu rapidly binds to and kills both Gram-negative and Gram-positive bacteria, without harming neighboring mammalian cells, as it does not disrupt the plasma membrane from the outside due to lipid-binding specificity. Under cell culture conditions, also active against intracellular bacteria, such as Listeria monocytogenes. Strongly binds to bacterial and mitochondrial lipids, including cardiolipin. Does not bind to unphosphorylated phosphatidylinositol, phosphatidylethanolamine nor phosphatidylcholine. Gasdermin D has been suggested to act as a tumor suppressor. Note: This description may include information from UniProtKB.
