Structure of the Rho-activating domain of Escherichia coli cytotoxic necrotizing factor 1
Structure of the Rho-activating domain of Escherichia coli cytotoxic necrotizing factor 1
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DOI：
10.1038/89610
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发表时间：
2001-07-01
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影响因子：
--
通讯作者：
Ghosh, P
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文献类型：
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作者：
Buetow, L;Flatau, G;Ghosh, P
某些致泌尿系疾病和新生儿脑膜炎的大肠杆菌菌株表达一种114 kDa的蛋白毒素，称为细胞毒性坏死因子1（CNF 1）。该毒素引起宿主细胞肌动蛋白细胞骨架的改变，并促进细菌侵入血脑屏障内皮细胞。CNF 1属于一组独特的大细胞毒素，其引起Rho鸟苷三磷酸酶（GTP酶）的组成性激活，所述GTP酶是肌动蛋白细胞骨架的关键调节剂。这个群体还包括E。大肠杆菌细胞毒性坏死因子2（CNF 2，114 kDa）和博德特氏菌属的皮肤坏死毒素（DNT，159 kDa）。与耶尔森氏菌属（Yersinia spp.）在这里，我们表明，CNF 1的催化区域表现出一种新的蛋白质折叠，由其1.83埃分辨率的晶体结构确定。结构揭示CNF 1具有Cys-His-主链氧催化三联体，这让人想起属于催化三联体超家族的酶。深口袋底部的催化Cys残基的位置限制了对潜在底物的接触，并有助于解释这种毒素和相关毒素的高度特异性。
Certain uropathogenic and neonatal meningitis-causing strains of Escherichia coli express a 114 kDa protein toxin called cytotoxic necrotizing factor 1 (CNF1). The toxin causes alteration of the host cell actin cytoskeleton and promotes bacterial invasion of blood-brain barrier endothelial cells. CNF1 belongs to a unique group of large cytotoxins that cause constitutive activation of Rho guanosine triphosphatases (GTPases), which are key regulators of the actin cytoskeleton. This group also includes E. coli cytotoxic necrotizing factor 2 (CNF2, 114 kDa) and dermonecrotic toxins (DNT, 159 kDa) of Bordetella spp. with related sequences occuring in Yersinia spp. Here we show that the catalytic region of CNF1 exhibits a novel protein fold as determined by its 1.83 Angstrom resolution crystal structure. The structure reveals that CNF1 has a Cys-His-main chain oxygen catalytic triad reminiscent of enzymes belonging to the catalytic triad superfamily. The position of the catalytic Cys residue at the base of a deep pocket restricts access to potential substrates and helps explain the high specificity of this and related toxins.