Ye E. WU, Weizhe HONG, Chong LIU, Lingqing ZHANG, and Zengyi CHANG (2008) “Conserved amphiphilic feature is essential for periplasmic chaperone HdeA to support acid resistance in enteric bacteria” Biochem. J. 412:389-397.

Abstract

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.

中文翻译

      题目：细胞膜间质蛋白HdeA保守的双亲性特征为其支持肠道细菌抗酸功能所必须

      摘要：哺乳动物胃部的极端酸性环境 (pH 1-3)对于像大肠杆菌、志贺氏菌和布鲁氏菌这样的肠道致病细菌而言是一种胁迫性的挑战。hdeA (hns-dependent expression A)基因被发现是这些肠道细菌在极端酸性条件下生存所必须的。我们最近的工作表明，HdeA蛋白只在像胃里那样的极端酸性条件下才表现出类分子伴侣活性，发挥这样的功能依赖于HdeA蛋白在低pH值（低于3）条件下其折叠完整的三维空间构象转变成一种去折叠的构象。本研究旨在揭示HdeA蛋白以这样的去折叠结构状态发挥功能的作用机制和背后的结构特征。我们的研究表明，HdeA蛋白保守的“双亲（亲水亲脂）”特征——即去折叠后暴露的疏水特征和肽链两个末端区域的高度带电特征——为其在极端酸性条件下发挥分子伴侣活性所必须；通过基因突变破坏这样的“双亲”特征后，大大减弱其分子伴侣活性。我们的研究也表明，HdeA蛋白的酸诱导分子伴侣活性对于肠道细菌的耐酸特征是非常重要的。另外，我们对HdeA蛋白这种双亲性结构特征的认识将帮助我们更好地理解其去折叠的（无规）构象为什么能否发挥其生物学功能。

      吴叶同学是永利官网2003级本科生，2005年通过北京大学的“泰兆” 本科科研基金进入昌增益教授实验室开展科研工作。她是一位非常刻苦勤奋、能够独立开展科研工作的优秀学生，其学习成绩在其所在年级名列前茅。吴叶同学目前在美国斯坦福大学(Stanford University)攻读博士学位。

      Biochemical Journal是英国生物化学学会主办的权威学术刊物，为生物化学领域历史最悠久的刊物，目前的SCI影响因子为4.1。