Bile salts are secreted into the gastrointestinal tract to aid in the absorption of lipids. In addition, bile salts show potent antimicrobial activity in part by mediating bacterial protein unfolding and aggregation. Here, using a protein folding sensor, we made the surprising discovery that the Escherichia coli periplasmic glycerol‐3‐phosphate (G3P)‐binding protein UgpB can serve, in the absence of its substrate, as a potent molecular chaperone that exhibits anti‐aggregation activity against bile salt‐induced protein aggregation. The substrate G3P, which is known to accumulate in the later compartments of the digestive system, triggers a functional switch between UgpB's activity as a molecular chaperone and its activity as a G3P transporter. A UgpB mutant unable to bind G3P is constitutively active as a chaperone, and its crystal structure shows that it contains a deep surface groove absent in the G3P‐bound wild‐type UgpB. Our work illustrates how evolution may be able to convert threats into signals that first activate and then inactivate a chaperone at the protein level in a manner that bypasses the need for ATP.

中文翻译：

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代谢物结合蛋白作为胆汁反应性伴侣蛋白。

胆汁盐会分泌到胃肠道中，以帮助吸收脂质。此外，胆汁盐部分通过介导细菌蛋白质的解折叠和聚集而显示出有效的抗菌活性。在这里，使用蛋白质折叠传感器，我们惊人地发现大肠杆菌周质 3-磷酸甘油 (G3P) 结合蛋白 UgpB 在没有底物的情况下可以作为一种有效的分子伴侣，对胆盐诱导的蛋白质聚集具有抗聚集活性。已知底物 G3P 会积聚在消化系统的后期隔室中，触发 UgpB 作为分子伴侣的活动与其作为 G3P 转运蛋白的活动之间的功能转换。不能结合 G3P 的 UgpB 突变体作为分子伴侣具有组成型活性，其晶体结构表明它包含 G3P 结合的野生型 UgpB 中不存在的深表面凹槽。我们的工作说明了进化如何能够将威胁转化为信号，这些信号首先激活，然后以绕过对 ATP 需求的方式在蛋白质水平上使伴侣蛋白失活。