Figure 6. Model of membrane pore formation by GSDMDNT.
After proteolytic cleavage, GSDMDNT monomers bind the inner leaflet of the plasma membrane. Aided by specific lipid interactions they multimerize and, at a critical size, spontaneously insert into the membrane. Depending on the concentration of membrane adhered GSDMDNT, the insertion may proceed either from a fully formed prepore ring or from small oligomeric assemblies. Dotted arrows indicate that the mechanism of β-sheet insertion so far remains unresolved. Pores formed by small oligomers cause early nonspecific ion flux and can combine with one another or grow sequentially by the attachment of uninserted monomers. Depending on the edge tension in the cellular milieu, arcs would continue to grow or crack to form slit-shaped pores (bottom). Whether slit-shaped pores can grow to circular pores by subsequent mono- or oligomer attachment is unclear.