The cell envelope is an integral and essential component of Gram-negative bacteria. As the front line during host–pathogen interactions, it is directly challenged by host immune responses as well as other harsh extracellular stimuli. The high permeability of the outer-membrane and the lack of ATP energy system render it difficult to maintain important biological activities within the periplasmic space under stress conditions. The HdeA/B chaperone machinery is the only known acid resistant system found in bacterial periplasm, enabling enteric pathogens to survive through the highly acidic human stomach and establish infections in the intestine. These two homologous chaperones belong to a fast growing family of conditionally disordered chaperones that conditionally lose their well-defined three-dimensional structures to exert biological activities. Upon losing ordered structures, these proteins commit promiscuous binding of diverse clients in response to environmental stimulation. For example, HdeA and HdeB are well-folded inactive dimers at neutral pH but become partially unfolded to protect a wide array of acid-denatured proteins upon acid stress. Whether these conditionally disordered chaperones possess client specificities remains unclear. This is in part due to the lack of efficient tools to investigate such versatile and heterogeneous protein–protein interactions under living conditions.

中文翻译：

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基因编码的光交联剂揭示了条件伴侣-客户的相互作用。

细胞包膜是革兰氏阴性细菌必不可少的组成部分。作为宿主与病原体相互作用的第一线，它直接受到宿主免疫反应以及其他苛刻的细胞外刺激的挑战。外膜的高渗透性和ATP能量系统的缺乏使得在压力条件下很难在周质空间内维持重要的生物活性。HdeA / B分子伴侣机制是在细菌周质中发现的唯一已知的耐酸系统，可使肠病原体在高酸性人胃中存活并在肠道中建立感染。这两个同源伴侣属于一个快速增长的有条件无序伴侣家族，有条件地失去了它们明确定义的三维结构以发挥生物活性。一旦失去有序的结构，这些蛋白质就会响应环境刺激而与各种客户混杂结合。例如，HdeA和HdeB在中性pH下是折叠良好的非活性二聚体，但在酸胁迫下会部分展开以保护各种各样的酸变性蛋白质。这些条件紊乱的伴侣分子是否具有客户特异性仍不清楚。部分原因是缺乏有效的工具来研究在生活条件下这种多功能和异质性的蛋白质间相互作用。HdeA和HdeB在中性pH下是折叠良好的非活性二聚体，但在酸性胁迫下会部分展开以保护各种各样的酸性变性蛋白质。这些条件紊乱的伴侣分子是否具有客户特异性仍不清楚。部分原因是缺乏有效的工具来研究在生活条件下这种多功能和异质性的蛋白质间相互作用。HdeA和HdeB在中性pH下是折叠良好的非活性二聚体，但在酸性胁迫下会部分展开以保护各种各样的酸性变性蛋白质。这些条件紊乱的伴侣分子是否具有客户特异性仍不清楚。部分原因是缺乏有效的工具来研究在生活条件下这种多功能和异质性的蛋白质间相互作用。