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-Structure paper
| タイトル | Cleavage-independent activation of ancient eukaryotic gasdermins and structural mechanisms. |
|---|---|
| ジャーナル・号・ページ | Science, Vol. 384, Issue 6697, Page adm9190, Year 2024 |
| 掲載日 | 2024年5月17日 |
著者 | Yueyue Li / Yanjie Hou / Qi Sun / Huan Zeng / Fanyi Meng / Xiang Tian / Qun He / Feng Shao / Jingjin Ding / ![]() |
| PubMed 要旨 | Gasdermins (GSDMs) are pore-forming proteins that execute pyroptosis for immune defense. GSDMs are two-domain proteins activated by proteolytic removal of the inhibitory domain. In this work, we ...Gasdermins (GSDMs) are pore-forming proteins that execute pyroptosis for immune defense. GSDMs are two-domain proteins activated by proteolytic removal of the inhibitory domain. In this work, we report two types of cleavage-independent GSDM activation. First, GSDM, a pore-forming domain-only protein from the basal metazoan , is a disulfides-linked autoinhibited dimer activated by reduction of the disulfides. The cryo-electron microscopy (cryo-EM) structure illustrates the assembly mechanism for the 44-mer GSDM pore. Second, RCD-1-1 and RCD-1-2, encoded by the polymorphic () gene in filamentous fungus , are also pore-forming domain-only GSDMs. RCD-1-1 and RCD-1-2, when encountering each other, form pores and cause pyroptosis, underlying allorecognition in . The cryo-EM structure reveals a pore of 11 RCD-1-1/RCD-1-2 heterodimers and a heterodimerization-triggered pore assembly mechanism. This study shows mechanistic diversities in GSDM activation and indicates versatile functions of GSDMs. |
リンク | Science / PubMed:38662913 |
| 手法 | EM (単粒子) / X線回折 |
| 解像度 | 1.86 - 3.63 Å |
| 構造データ | EMDB-36732, PDB-8jyw: ![]() EMDB-36733: Cryo-EM structure of the gasdermin pore from Trichoplax adhaerens EMDB-36734, PDB-8jyz: ![]() PDB-8jyv: ![]() PDB-8jyx: ![]() PDB-8jyy: |
| 化合物 | ![]() ChemComp-HOH: |
| 由来 |
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キーワード | IMMUNE SYSTEM / Pyroptosis / Gasdermnin / Ggasdermin / Pore-forming / Allorecognition / Pore |
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neurospora crassa (菌類)
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