GSDMD forms ring‐shaped oligomers

Stable Identifier
Reaction [binding]
Homo sapiens
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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).

Literature References
PubMed ID Title Journal Year
29898893 Mechanism of membrane pore formation by human gasdermin-D

Pfreundschuh, M, Mari, SA, Sborgi, L, Hiller, S, Müller, DJ, Mulvihill, E

EMBO J. 2018
27418190 GSDMD membrane pore formation constitutes the mechanism of pyroptotic cell death

Broz, P, Heilig, R, Pipercevic, J, Rühl, S, Sborgi, L, Farady, CJ, Stahlberg, H, Hiller, S, Müller, DJ, Mulvihill, E

EMBO J. 2016
27281216 Pore-forming activity and structural autoinhibition of the gasdermin family

Wang, DC, Ding, J, Liu, W, Shi, J, Shao, F, Wang, K, Sun, Q, Sun, H, She, Y

Nature 2016
This event is regulated
Orthologous Events
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