BPS2026 – Characterization of metal ion influence on GSDMD

GSDMD is the key executioner of pyroptotic cell death. Upon cleavage and release from the inhibitory C-terminal domain (CTD), through the action of inflammatory caspases, the unstructured loops of the N-terminal domain (NTD) become the membrane-inserted beta sheets of an oligomeric GSDMD pore structure. This dramatic structural rearrangement from monomer to oligomers of the GSDMD NTDs results in large membrane pores that allow the influx of ions and efflux of pro-inflammatory cytokines, leading to the amplification of the pathway and eventual cell death. Here, we investigated how metal ions can bind and influence these transitions of GSDMD using purified components and biophysical techniques such as DLS, DSF, and SPR.