EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Structural basis for GSDMB pore formation and its targeting by IpaH7.8.
ジャーナル・号・ページ	Nature, Vol. 616, Issue 7957, Page 590-597, Year 2023
掲載日	2023年3月29日
著者	Chengliang Wang / Sonia Shivcharan / Tian Tian / Skylar Wright / Danyang Ma / JengYih Chang / Kunpeng Li / Kangkang Song / Chen Xu / Vijay A Rathinam / Jianbin Ruan /
PubMed 要旨	Gasdermins (GSDMs) are pore-forming proteins that play critical roles in host defence through pyroptosis. Among GSDMs, GSDMB is unique owing to its distinct lipid-binding profile and a lack of ...Gasdermins (GSDMs) are pore-forming proteins that play critical roles in host defence through pyroptosis. Among GSDMs, GSDMB is unique owing to its distinct lipid-binding profile and a lack of consensus on its pyroptotic potential. Recently, GSDMB was shown to exhibit direct bactericidal activity through its pore-forming activity. Shigella, an intracellular, human-adapted enteropathogen, evades this GSDMB-mediated host defence by secreting IpaH7.8, a virulence effector that triggers ubiquitination-dependent proteasomal degradation of GSDMB. Here, we report the cryogenic electron microscopy structures of human GSDMB in complex with Shigella IpaH7.8 and the GSDMB pore. The structure of the GSDMB-IpaH7.8 complex identifies a motif of three negatively charged residues in GSDMB as the structural determinant recognized by IpaH7.8. Human, but not mouse, GSDMD contains this conserved motif, explaining the species specificity of IpaH7.8. The GSDMB pore structure shows the alternative splicing-regulated interdomain linker in GSDMB as a regulator of GSDMB pore formation. GSDMB isoforms with a canonical interdomain linker exhibit normal pyroptotic activity whereas other isoforms exhibit attenuated or no pyroptotic activity. Overall, this work sheds light on the molecular mechanisms of Shigella IpaH7.8 recognition and targeting of GSDMs and shows a structural determinant in GSDMB critical for its pyroptotic activity.
リンク	Nature / PubMed:36991122 / PubMed Central
手法	EM (単粒子)
解像度	3.8 - 4.96 Å
構造データ	28087 8efp EMDB-28087, PDB-8efp: CryoEM structure of GSDMB in complex with shigella IpaH7.8 手法: EM (単粒子) / 解像度: 3.8 Å 28583 8et1 EMDB-28583, PDB-8et1: CryoEM structure of GSDMB pore without transmembrane beta-barrel 手法: EM (単粒子) / 解像度: 4.48 Å 28584 8et2 EMDB-28584, PDB-8et2: CryoEM structure of the GSDMB pore 手法: EM (単粒子) / 解像度: 4.96 Å
由来	shigella flexneri (フレクスナー赤痢菌) homo sapiens (ヒト)
キーワード	TRANSFERASE/LIPID BINDING PROTEIN / GSDMB / GSDMD / pyroptosis / ubiquitination (ユビキチン) / ANTIMICROBIAL PROTEIN (抗微生物ペプチド) / TRANSFERASE-LIPID BINDING PROTEIN complex / IMMUNE SYSTEM (免疫系) / Pore-forming protein (膜孔形成毒素)