. Author manuscript; available in PMC: 2023 Feb 28.

Published in final edited form as: J Mol Biol. 2021 Oct 8;434(4):167297. doi: 10.1016/j.jmb.2021.167297

Table 1.

Summary of GSDMs activation and regulation

Human GSDMs	Mouse GSDMs	Pore-formation	Pore-size	Proteolytic Activation	Proteolytic Inhibition	Post-translational modifications	Ref.
GSDMA	GSDMA1–3	Yes	26–28 mer; 28 nm (outer) and 18 nm (inner) (27-mer)^a	Unknown	Unknown	Phosphorylation of Thr8 by PLK1 inhibits pore-forming activity.	[22, 99]
GSDMB	None	Yes	13.5 – 15.6 nm (inner)^b	Caspase-1/3/6/7; Granzyme A	Unknown	Ubiquitination by IpaH7.8 mediates 26S proteasome degradation.	[22, 37, 79, 92]
GSDMC	GSDMC1–4	Yes	Unknown	Caspase-8	Unknown	Unknown	[22, 36]
GSDMD	GSDMD	Yes	31–34 mer; 31.5 nm (outer) and 21.5 nm (inner) (33-mer)^a	Caspase-1/4/5/11, Caspase-8; neutrophil elastase; cathepsin G;	Caspase-3/7, Pathogen proteases	Itaconation of Cys77 and succination of Cys56/191/268/309/467 inhibit pore-forming activity; Phosphorylation of Tyr37/158 and Ser185 with unknown function.	[19–22, 72–76, 95–98, 100, 103]
GSDME (DFNA5)	GSDME (DFNA5)	Yes	Unknown	Caspase-3; Caspase-1/7^c; Granzyme B	Unknown	Phosphorylation of Thr6 inhibits pore-forming activity; Palmitoylation of Cys407 and Cys408 enhances pore-forming activity.	[22, 34, 35, 38, 78, 99, 101]
GSDMF (DFNB59 or PJVK)	GSDMF (DFNB59 or PJVK)	Unknown	Unknown	Unknown	Unknown	Unknown

^a:

The pore sizes are measured based on the cryo-EM structures; the outer and inner diameters are shown, respectively;

^b:

The pore size is based on the negative-stain EM measurement; the average of the inner diameter is shown.

^c:

The cleavage of GSDME by caspase-1 and -7 is currently observed only in teleosts.