Gasdermin D N-terminal fragment (GSDMD-NT)

Gasdermin D N-terminal fragment (GSDMD-NT) is the pore-forming domain generated by caspase-1 or caspase-11 cleavage of full-length gasdermin D (GSDMD). Upon inflammasome activation, GSDMD is cleaved, releasing the N-terminal fragment that translocates to the plasma membrane, oligomerizes, and forms large pores (10–15 nm) in the membrane, resulting in pyroptosis, a lytic, pro-inflammatory form of cell death, and facilitating the release of pro-inflammatory cytokines such as IL-1β and IL-18[3][5][7]. GSDMD-NT is selective for inner leaflet phospholipids, sparing intact host membranes from extracellular attack. Recent studies also reveal that GSDMD-NT exerts negative feedback on inflammation by directly inhibiting caspase-1/11, dependent on its RFWK motif[4][5]. Post-translational modifications like ubiquitination and succinylation critically regulate its membrane localization and pore-forming activity, representing potential regulatory or therapeutic intervention points[6]. GSDMD-NT is implicated as both a drug target and a biomarker for pyroptosis-related diseases, including sepsis, inflammatory disorders, and infection[3][4][5][6].

Other names

Gasdermin D N-terminal domainGSDMD-NGD-NT

Inhibition of N-terminal fragment ubiquitination blocks membrane translocation and pyroptosis[6]; Peptide inhibitors derived from the RFWK motif can block caspase-1/11 activation and downstream inflammation[4][5]