Structural basis for virulence regulation in Vibrio cholerae by unsaturated fatty acid components of bile
Structural basis for virulence regulation in Vibrio cholerae by unsaturated fatty acid components of bile
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DOI：
10.1038/s42003-019-0686-x
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发表时间：
2019-11-28
影响因子：
5.9
通讯作者：
Kull, F. Jon
中科院分区：
文献类型：
--
作者：
Cruite, Justin T.;Kovacikova, Gabriela;Kull, F. Jon
AraC/XylS家族转录调节因子ToxT是霍乱弧菌的主要毒力激活因子，霍乱弧菌是引起霍乱的革兰氏阴性细菌病原体。胆汁中发现的不饱和脂肪酸（UFA）抑制ToxT的活性。已报道了与乌法或合成抑制剂结合的受抑制的ToxT的晶体结构，但尚未确定活性构象的ToxT的结构。在这里，我们提出了2.5埃结构的ToxT没有抑制剂。该结构表明乌法或抑制剂的释放导致柔性增加，从而允许ToxT采用能够二聚化和结合DNA的活性构象。小角X-射线散射被用来验证一个开放的ToxT二聚体结合到霍乱毒素启动子的结构模型。本研究结果提供了胆汁中乌法组分和其他合成ToxT抑制剂对霍乱弧菌毒力基因调控的详细结构机制。
The AraC/XylS-family transcriptional regulator ToxT is the master virulence activator of Vibrio cholerae, the gram-negative bacterial pathogen that causes the diarrheal disease cholera. Unsaturated fatty acids (UFAs) found in bile inhibit the activity of ToxT. Crystal structures of inhibited ToxT bound to UFA or synthetic inhibitors have been reported, but no structure of ToxT in an active conformation had been determined. Here we present the 2.5 angstrom structure of ToxT without an inhibitor. The structure suggests release of UFA or inhibitor leads to an increase in flexibility, allowing ToxT to adopt an active conformation that is able to dimerize and bind DNA. Small-angle X-ray scattering was used to validate a structural model of an open ToxT dimer bound to the cholera toxin promoter. The results presented here provide a detailed structural mechanism for virulence gene regulation in V. cholerae by the UFA components of bile and other synthetic ToxT inhibitors.