Growing a gasdermin pore in membranes of pyroptotic cells

Abstract

Inflammasome‐activated caspase‐1, caspase‐11, caspase‐4, and caspase‐5 cleave GSDMD to unleash its N‐terminal gasdermin‐N domain (GSDMD^{N term}) that perforates the plasma membrane to execute pyroptosis and stimulate inflammation. The mechanism underlying GSDMD^{N term} pore formation is unclear. Mulvihill et al use high‐resolution atomic force microscopy (AFM) to analyze the dynamic pore formation process of GSDMD^{N term}. GSDMD^{N term} protomers are inserted into the lipid membrane to assemble arc‐ or slit‐shaped oligomers that can incorporate additional protomers and grow into large and stable ring‐shaped oligomers to form pores.