The cell death program pyroptosis plays an important role in the development and homeostasis of multicellular organisms. It is also a root cause for inflammatory damage in tissues ranging from the endothelium to cardiovascular tissues. Canonical upstream activation of caspase-1 in humans and caspase-11 in mice triggers this lytic program via the cleavage of gasdermins. Activated Gasdermin D (GSDMD) forms ~21 nm diameter oligomeric pores in the plasma membrane causing osmotic imbalance, cell lysis, and driving the release of pro-inflammatory cytokines IL-1β and IL-18, to promote downstream T cell and macrophage activation responses. It has been hypothesized that biochemical signals can shut these pores after their formation and resume by opening on the short seconds/minutes time scale, thereby modulating the progression of pyroptosis.
Interestingly, gasdermins are relatively conserved, being present in very simple organisms. Here you have a recent cryoEM structure of gasdermin pore from Trichoplax adhaerens, a very simple metazoan (PDB code: 8JYW)

#scivis #sciart #molecularart #gasdermin #pyroptosis #pore #dynamics #cryoem

Structure rendered with @proteinimaging, post-processed with @stylar.ai_official and depicted with @corelphotopaint