GSDMD forms ring‐shaped oligomers

Stable Identifier
R-HSA-9647619
Type
Reaction [binding]
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

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
27418190 GSDMD membrane pore formation constitutes the mechanism of pyroptotic cell death

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

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

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

Nature 2016
Participants
Participates
This event is regulated
Orthologous Events
Authored
Reviewed
Created
Cite Us!