Function
Gasdermin (GSDM) is the substrate of the inflammatory Caspase downstream from inflammasomes which activate caspase. Inflammasomes are supramolecular signalling assemblies activating the lytic process against exogenous pathogens. GSDM is required for cytokine release and pyroptosis, a lytic form of programmed cell death) [1]. Pyropptosis is the regulated lytic cell death mediated by GSMD pore formation. GSDM D contains 2 domains: the N-terminal fragment which is pore-forming and the repressive C-terminal. The GSDM family contains 6 members in human.
- Gasdermin D is a pore-forming protein involved in cell death of macrophages[2].
Disease
GSDM is implicated in autoimmune diseases and certain cancers.
Relevance
Because of its potential as a driver of inflammation in septic shock and autoimmune diseases GSMD D is an attractive drug target[3], [4].
Structural highlights
The 3D structure of GSDM A3 shows the monomer of the pore formed by the N-terminal of the molecule. Each subunit contributes 4 long β strands to the transmembrane region of the pore. The pore is formed by 27-fold symmetry[5].
3D structures of gasdermin
Gasdermin 3D structures
