cleaved N-terminal DFNA5 / GSDME Recombinant Rabbit mAb (S-6129)

Cleaved N-terminal DFNA5/GSDME (also known as GSDME-NT) is the active N-terminal fragment released after proteolytic cleavage of the gasdermin E protein, and it is the key executor molecule that converts full-length GSDME from non-inflammatory apoptosis to pyroptosis. Full-length GSDME is normally maintained in an autoinhibited state through intramolecular interactions between its N-terminal and C-terminal domains and lacks pore-forming activity. When apoptotic signaling activates caspase-3, or when cytotoxic lymphocytes deliver granzyme B (GZMB), GSDME is cleaved after aspartate at position 270, releasing an N-terminal fragment of approximately 30–35 kDa. This fragment then translocates to the inner leaflet of the plasma membrane, binds phosphoinositides such as PIP2, undergoes homo-oligomerization, and inserts into the membrane to form transmembrane pores with an inner diameter of approximately 10–15 nm, leading to cell swelling, membrane rupture, and release of intracellular contents (including IL-1β), thereby triggering pyroptosis. In addition to the plasma membrane, GSDME-NT can also permeabilize mitochondrial membranes, promoting cytochrome c release and further amplifying apoptosome-dependent caspase-3 activation, forming a feed-forward amplification loop. In tumor biology, GSDME-NT-mediated pyroptosis can enhance antitumor immunity and suppress tumor growth, whereas GSDME expression is often silenced in various tumors due to promoter methylation.