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Bacterial gasdermins reveal an ancient mechanism of cell death.

ABSTRACT: Gasdermin proteins form large membrane pores in human cells that release immune cytokines and induce lytic cell death. Gasdermin pore formation is triggered by caspase-mediated cleavage during inflammasome signaling and is critical for defense against pathogens and cancer. We discovered gasdermin homologs encoded in bacteria that defended against phages and executed cell death. Structures of bacterial gasdermins revealed a conserved pore-forming domain that was stabilized in the inactive state with a buried lipid modification. Bacterial gasdermins were activated by dedicated caspase-like proteases that catalyzed site-specific cleavage and the removal of an inhibitory C-terminal peptide. Release of autoinhibition induced the assembly of large and heterogeneous pores that disrupted membrane integrity. Thus, pyroptosis is an ancient form of regulated cell death shared between bacteria and animals.

SUBMITTER: Johnson AG

PROVIDER: S-EPMC9134750 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Bacterial gasdermins reveal an ancient mechanism of cell death.

Johnson Alex G AG Wein Tanita T Mayer Megan L ML Duncan-Lowey Brianna B Yirmiya Erez E Oppenheimer-Shaanan Yaara Y Amitai Gil G Sorek Rotem R Kranzusch Philip J PJ

Science (New York, N.Y.) 20220113 6577

Gasdermin proteins form large membrane pores in human cells that release immune cytokines and induce lytic cell death. Gasdermin pore formation is triggered by caspase-mediated cleavage during inflammasome signaling and is critical for defense against pathogens and cancer. We discovered gasdermin homologs encoded in bacteria that defended against phages and executed cell death. Structures of bacterial gasdermins revealed a conserved pore-forming domain that was stabilized in the inactive state w ...[more]

PMID: 35025633

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