+検索条件
-Structure paper
タイトル | Structure and assembly of a bacterial gasdermin pore. |
---|---|
ジャーナル・号・ページ | Nature, Vol. 628, Issue 8008, Page 657-663, Year 2024 |
掲載日 | 2024年3月20日 |
著者 | Alex G Johnson / Megan L Mayer / Stefan L Schaefer / Nora K McNamara-Bordewick / Gerhard Hummer / Philip J Kranzusch / |
PubMed 要旨 | In response to pathogen infection, gasdermin (GSDM) proteins form membrane pores that induce a host cell death process called pyroptosis. Studies of human and mouse GSDM pores have revealed the ...In response to pathogen infection, gasdermin (GSDM) proteins form membrane pores that induce a host cell death process called pyroptosis. Studies of human and mouse GSDM pores have revealed the functions and architectures of assemblies comprising 24 to 33 protomers, but the mechanism and evolutionary origin of membrane targeting and GSDM pore formation remain unknown. Here we determine a structure of a bacterial GSDM (bGSDM) pore and define a conserved mechanism of pore assembly. Engineering a panel of bGSDMs for site-specific proteolytic activation, we demonstrate that diverse bGSDMs form distinct pore sizes that range from smaller mammalian-like assemblies to exceptionally large pores containing more than 50 protomers. We determine a cryo-electron microscopy structure of a Vitiosangium bGSDM in an active 'slinky'-like oligomeric conformation and analyse bGSDM pores in a native lipid environment to create an atomic-level model of a full 52-mer bGSDM pore. Combining our structural analysis with molecular dynamics simulations and cellular assays, our results support a stepwise model of GSDM pore assembly and suggest that a covalently bound palmitoyl can leave a hydrophobic sheath and insert into the membrane before formation of the membrane-spanning β-strand regions. These results reveal the diversity of GSDM pores found in nature and explain the function of an ancient post-translational modification in enabling programmed host cell death. |
リンク | Nature / PubMed:38509367 |
手法 | EM (単粒子) |
解像度 | 3.3 - 7.3 Å |
構造データ | EMDB-40570, PDB-8sl0: EMDB-43508: Structure of a bacterial gasdermin small oval pore assembly EMDB-43509: Structure of a bacterial gasdermin medium oval pore assembly EMDB-43510: Structure of a bacterial gasdermin large oval pore assembly EMDB-43511: Structure of a bacterial gasdermin double pore assembly EMDB-43513: Structure of a bacterial gasdermin slinky-like oligomer from a heterogeneous sample |
由来 |
|
キーワード | IMMUNE SYSTEM / viral mimicry / gasdermin / caspase / autoinhibition / pyroptosis / bats / immunity / cell death |