GSDMD (1-275) binds PIPs

Stable Identifier
R-HSA-9647631
Type
Reaction [binding]
Species
Homo sapiens
Compartment
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Human gasdermin D (GSDMD) is a member of the gasdermin (GSDM) protein family, which is processed by inflammatory caspases and cleaved into N‑terminal (GSDMD(1‑275)) and C‑terminal (GSDMD(276‑484)) fragments (Shi et al. 2015). The N‑terminal fragment of GSDMD (1‑275) by itself caused pyroptosis when expressed ectopically in human embryonic kidney HEK293 cells, whereas the overexpression of the GSDMD C‑terminus was found to block pyroptosis (Shi et al, 2015). The N‑terminal fragment, GSDMD (1‑275), targets and permeabilizes cellular membranes by assembling transmembrane pores (Ding et al, 2016; Liu X et al, 2016; Sborgi et al, 2016; Mulvihill et al. 2018). High‐resolution (≤ 2 nm) atomic force microscopy (AFM) showed that the N‑terminal fragment of GSDMD inserts into various lipid membranes (Mulvihill E et al. 2018). The lipid composition of the membrane was found to directly influence the ability of GSDMD to permeabilize liposomes (Ding et al, 2016; Liu et al, 2016; Mulvihill et al. 2018). Whereas phosphoinositides (PIPs) facilitated binding of GSDMD (1‑275), cholesterol reduced insertion of GSDMD (1‑275) and pore formation (Ding et al, 2016; Sborgi et al, 2016; Mulvihill et al. 2018). Once inserted, GSDMD (1‑275) assembles arc‐, slit‐, and ring‐shaped oligomers (Ding et al, 2016; Liu et al, 2016; Sborgi et al, 2016; Mulvihill et al. 2018).

Literature References
PubMed ID Title Journal Year
29990470 Mechanisms of Gasdermin Family Members in Inflammasome Signaling and Cell Death

Feng, S, Fox, D, Man, SM

J. Mol. Biol. 2018
29898893 Mechanism of membrane pore formation by human gasdermin-D

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

EMBO J. 2018
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