Bacterial gasdermins reveal an ancient mechanism of cell death.
Saved in:
| Title: | Bacterial gasdermins reveal an ancient mechanism of cell death. |
|---|---|
| Authors: | Johnson, Alex G., Wein, Tanita, Mayer, Megan L., Duncan-Lowey, Brianna, Yirmiya, Erez, Oppenheimer-Shaanan, Yaara, Amitai, Gil, Sorek, Rotem, Kranzusch, Philip J. |
| Source: | Science (pre-March 2025). 1/14/2022, Vol. 375 Issue 6577, p221-225. 5p. 4 Diagrams. |
| Subjects: | Cell death, Cytokines, Inflammasomes, Bacteria, Bacteriophages |
| 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. [ABSTRACT FROM AUTHOR] |
| Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Psychology and Behavioral Sciences Collection |
|
Full text is not displayed to guests.
Login for full access.
|
|
| 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. [ABSTRACT FROM AUTHOR] |
|---|---|
| ISSN: | 00368075 |
| DOI: | 10.1126/science.abj8432 |
