Gasdermin D (GSDMD) is cleaved by inflammatory caspases into an N‐terminal (GSDMD(1-275)) and a C‐terminal (GSDMD (276-484)) fragment (Shi et al, 2015). The liposome-based assays indicated that the N-terminal doman of GSDMD (1-275) binds membrane lipids assembling large pores (Ding J et al. 2016; Liu X et al. 2016). High‐resolution (≤ 2 nm) atomic force microscopy (AFM) showed that the GSDMD N-terminus inserts into various lipid membranes (Mulvihill E et al. 2018). Once inserted, the N-terminal fragment of GSDMD assembles arc‐, slit‐, and ring‐shaped oligomers, which eventually can incorporate additional oligomers and transform into larger thermodynamically stable ring‐shaped oligomers (Mulvihill E et al. 2018). Ca2+ influx through GSDMD pores was shown to recruit the endosomal sorting complexes required for transport (ESCRT) machinery to damaged areas of the plasma membrane, leading to membrane repair. ESCRT-III–dependent membrane repair is thought to negatively regulate cell death and interleukin (IL)-1β, IL18 secretion following inflammasome activation (Rühl S et al. 2018).
Pfreundschuh, M, Mari, SA, Sborgi, L, Hiller, S, Müller, DJ, Mulvihill, E
Broz, P, Heilig, R, Pipercevic, J, Rühl, S, Sborgi, L, Farady, CJ, Stahlberg, H, Hiller, S, Müller, DJ, Mulvihill, E
Wang, DC, Ding, J, Liu, W, Shi, J, Shao, F, Wang, K, Sun, Q, Sun, H, She, Y
© 2023 Reactome
