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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, Page eadm9190, Year 2024
掲載日	2024年4月25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. Here we report two ...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. Here 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. Cryo-electron microscopy (cryo-EM) structure illustrates assembly mechanism for the 44-mer GSDM pore. Second, RCD-1-1/RCD-1-2, encoded by polymorphic 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 . Cryo-EM structure reveals a pore of 11 RCD-1-1/RCD-1-2 heterodimers and 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	36732 8jyw EMDB-36732, PDB-8jyw: Cryo-EM structure of the gasdermin pore from Trichoplax adhaerens 手法: EM (単粒子) / 解像度: 3.3 Å EMDB-36733: Cryo-EM structure of the gasdermin pore from Trichoplax adhaerens 手法: EM (単粒子) / 解像度: 3.34 Å 36734 8jyz EMDB-36734, PDB-8jyz: Cryo-EM structure of RCD-1 pore from Neurospora crassa 手法: EM (単粒子) / 解像度: 3.63 Å PDB-8jyv: Crystal structure of the gasdermin from Trichoplax adhaerens 手法: X-RAY DIFFRACTION / 解像度: 1.86 Å PDB-8jyx: Crystal structure of the gasdermin-like protein RCD-1-1 from Neurospora crassa 手法: X-RAY DIFFRACTION / 解像度: 2.35 Å PDB-8jyy: Crystal structure of the gasdermin-like protein RCD-1-2 from Neurospora crassa 手法: X-RAY DIFFRACTION / 解像度: 2.65 Å
化合物	ChemComp-HOH: WATER / 水
由来	trichoplax adhaerens (センモウヒラムシ) neurospora crassa (アカパンカビ) escherichia coli (大腸菌)
キーワード	IMMUNE SYSTEM (免疫系) / Pyroptosis / Gasdermnin / Ggasdermin / Pore-forming / Allorecognition / Pore