Conserved amphiphilic feature is essential for periplasmic chaperone HdeA to support acid resistance in enteric bacteria
Conserved amphiphilic feature is essential for periplasmic chaperone HdeA to support acid resistance in enteric bacteria
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保守的两亲特征对于周质伴侣 HdeA 支持肠道细菌的酸性抵抗至关重要
DOI：
10.1042/bj20071682
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发表时间：
2008-06-01
影响因子：
4.1
通讯作者：
Chang, Zengyi
中科院分区：
文献类型：
--
作者：
Wu, Ye E.;Hong, Weizhe;Chang, Zengyi
哺乳动物胃部的极酸性环境（pH 1-3）对肠道致病菌（包括大肠杆菌、志贺氏菌和布鲁氏菌）构成了严峻的挑战。 hdeA（hns 依赖性表达 A）基因被发现对于这些肠道细菌在极低 pH 条件下的生存至关重要。我们最近证明，HdeA 能够从较高 pH 值（高于 pH 3）下的良好折叠构象转变为极低 pH 值（低于 pH 3）下的未折叠构象，从而仅在胃 pH 范围内表现出类似伴侣的活性。本研究旨在表征 HdeA 在这种展开构象中发挥作用的作用机制和潜在的特定结构特征。在本研究中，我们证明了 HdeA 的保守“两亲”特征，即保守疏水区域和高电荷末端区域的暴露，对于在极低 pH 条件下表现出类伴侣活性至关重要。破坏这种两亲特征的突变显着降低了 HdeA 的分子伴侣活性。结果还强烈表明，HdeA 的这种酸诱导的分子伴侣样活性对于肠道细菌的耐酸性至关重要。此外，我们对 HdeA 的这种两亲结构特征的新理解有助于更好地解释这种展开（无序）构象如何发挥功能活性。
The extremely acidic environment of the mammalian stomach (pH 1-3) represents a stressful challenge for enteric pathogenic bacteria, including Escherichia coli, Shigella and Brucella. The hdeA (hns-dependent expression A) gene was found to be crucial for the survival of these enteric bacteria under extremely low pH conditions. We recently demonstrated that HdeA is able to exhibit chaperone-like activity exclusively within the stomach pH range by transforming from a well-folded conformation at higher pH values (above pH 3) into an unfolded conformation at extremely low pH values (below pH 3). This study was performed to characterize the action mechanisms and underlying specific structural features for HdeA to function in this unfolded conformation. In the present study, we demonstrate that the conserved 'amphiphilic' feature of HdeA, i.e. the exposure of the conserved hydrophobic region and highly charged terminal regions, is essential for exhibiting chaperone-like activity under extremely low pH conditions. Mutations that disrupt this amphiphilic feature markedly reduced the chaperone-like activity of HdeA. The results also strongly suggest that this acid-induced chaperone-like activity of HdeA is crucial for acid resistance of the enteric bacteria. Moreover, our new understanding of this amphiphilic structural feature of HdeA helps to better interpret how this unfolded (disordered) conformation could be functionally active.