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 (GSDMDNterm) that perforates the plasma membrane to execute pyroptosis and stimulate inflammation. The mechanism underlying GSDMDNterm pore formation is unclear. Mulvihill et al use high‐resolution atomic force microscopy (AFM) to analyze the dynamic pore formation process of GSDMDNterm. GSDMDNterm 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. The EMBO Journal (2018) e100067