Bacterial gasdermins reveal an ancient mechanism of cell death

Alex G. Johnson, Tanita Wein, Megan L. Mayer, Brianna Duncan-Lowey, Erez Yirmiya, Yaara Oppenheimer-Shaanan, Gil Amitai, Rotem Sorek*, Philip J. Kranzusch*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

98 Scopus citations

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.

Original languageAmerican English
Pages (from-to)221-225
Number of pages5
JournalScience
Volume375
Issue number6577
DOIs
StatePublished - 14 Jan 2022
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2022 American Association for the Advancement of Science. All rights reserved.

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