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	Activating and inhibiting nucleotide signals coordinate bacterial anti-phage defense.
ジャーナル・号・ページ	bioRxiv, Year 2025
掲載日	2025年7月9日
著者	Sonomi Yamaguchi / Samantha G Fernandez / Douglas R Wassarman / Marlen Lüders / Frank Schwede / Philip J Kranzusch /
PubMed 要旨	The cellular nucleotide pool is a major focal point of the host immune response to viral infection. Immune effector proteins that disrupt the nucleotide pool allow animal and bacterial cells to ...The cellular nucleotide pool is a major focal point of the host immune response to viral infection. Immune effector proteins that disrupt the nucleotide pool allow animal and bacterial cells to broadly restrict diverse viruses, but reduced nucleotide availability induces cellular toxicity and can limit host fitness(Ahmad et al., 1998; Goldstone et al., 2011; Hsueh et al., 2022; Itsko & Schaaper, 2014; Tal et al., 2022). Here we discover a bacterial anti-phage defense system named Clover that overcomes this tradeoff by encoding a deoxynucleoside triphosphohydrolase enzyme (CloA) that dynamically responds to both an activating phage cue and an inhibitory nucleotide immune signal produced by a partnering regulatory enzyme (CloB). Analysis of Clover phage restriction in cells and reconstitution of enzymatic function in vitro demonstrate that CloA is a dGTPase that responds to viral enzymes that increase cellular levels of dTTP. To restrain CloA activation in the absence of infection, we show that CloB synthesizes a dTTP-related inhibitory nucleotide signal p3diT (5'-triphosphothymidyl-3'5'-thymidine) that binds to CloA and suppresses activation. Cryo-EM structures of CloA in activated and suppressed states reveal how dTTP and p3diT control distinct allosteric sites and regulate effector function. Our results define how nucleotide signals coordinate both activation and inhibition of antiviral immunity and explain how cells balance defense and immune-mediated toxicity.
リンク	bioRxiv / PubMed:40672243 / PubMed Central
手法	EM (単粒子) / X線回折
解像度	2.37 - 2.68 Å
構造データ	71386 9p8s EMDB-71386, PDB-9p8s: Structure of CloA apo 手法: EM (単粒子) / 解像度: 2.37 Å 71388 9p8t EMDB-71388, PDB-9p8t: Structure of CloA co-expressed with CloB 手法: EM (単粒子) / 解像度: 2.65 Å 71389 9p8u EMDB-71389, PDB-9p8u: Structure of CloA in complex with dGTP and p3diT 手法: EM (単粒子) / 解像度: 2.56 Å 71390 9p8v EMDB-71390, PDB-9p8v: Structure of CloA in complex with dGTP and dTTP 手法: EM (単粒子) / 解像度: 2.59 Å PDB-9p8w: Anti-phage dGTPase from Shewanella putrefaciens CN-32 手法: X-RAY DIFFRACTION / 解像度: 2.68 Å
化合物	ChemComp-MG: Unknown entry / マグネシウムジカチオン ChemComp-DGT: 2'-DEOXYGUANOSINE-5'-TRIPHOSPHATE / dGTP ChemComp-TTP: THYMIDINE-5'-TRIPHOSPHATE / dTTP ChemComp-HOH: WATER
由来	salmonella enterica (サルモネラ菌) synthetic construct (人工物) shewanella putrefaciens cn-32 (バクテリア)
キーワード	HYDROLASE / deoxynucleoside triphosphohydrolase