Gasdermin-D (GSDMD)

Gasdermin-D, N-terminal: Promotes pyroptosis in response to microbial infection and risk signals. Produced by the cleavage of gasdermin-D by inflammatory caspases CASP1 or CASP4 in reaction to canonical, in addition to non-canonical (such as cytosolic LPS) inflammasome activators (PubMed:26375003, PubMed:26375259, PubMed:27418190).

After cleavage, moves to the plasma membrane where it strongly binds to inner leaflet lipids, including monophosphorylated phosphatidylinositols, such as phosphatidylinositol 4-phosphate, bisphosphorylated phosphatidylinositols, such as phosphatidylinositol (4,5)- bisphosphate, in addition to phosphatidylinositol (3,4,5)- bisphosphate, and more weakly to phosphatidic acid and phosphatidylserine (PubMed:27281216). Homooligomerizes inside the membrane and forms pores of 10 - 15 nanometers (nm) of inner diameter, possibly permitting the release of mature IL1B and triggering pyroptosis (PubMed:27418190, PubMed:27281216).