研究人员发现了在细菌中编码的gasdermin同源物，它们可以防御噬菌体并执行细胞死亡。细菌gasdermin的结构显示了一个保守的孔隙形成结构域，该结构域在非活性状态下被埋藏的脂质修饰所稳定。细菌gasdermin被类似于caspase的蛋白酶激活，这些蛋白酶催化特定部位的切割，并去除一个抑制性的C端肽。自身抑制的释放诱发了大型和异质性孔的组装，进而破坏了膜的完整性。因此，焦亡是细菌和动物之间共享的一种古老的调节细胞死亡形式。
据了解，gasdermin蛋白在人类细胞中形成大的膜孔，释放免疫细胞因子并诱导细胞死亡。gasdermin孔的形成是由炎症体信号传导过程中的caspase介导的切割引发的，对防御病原体和癌症至关重要。
附：英文原文
Title: Bacterial gasdermins reveal an ancient mechanism of cell death
Author: Alex G. Johnson, Tanita Wein, Megan L. Mayer, Brianna Duncan-Lowey, Erez Yirmiya, Yaara Oppenheimer-Shaanan, Gil Amitai, Rotem Sorek, Philip J. Kranzusch
Issue&Volume: 2022-01-14
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.
DOI: abj8432
Source: https://www.science.org/doi/10.1126/science.abj8432