Probing the Structure of the Escherichia coli Periplasmic Proteins HdeA and YmgD by Molecular Dynamics Simulations
Probing the Structure of the Escherichia coli Periplasmic Proteins HdeA and YmgD by Molecular Dynamics Simulations
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DOI：
10.1021/acs.jpcb.6b06091
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发表时间：
2016-11-24
影响因子：
3.3
通讯作者：
Sticht, Heinrich
中科院分区：
文献类型：
--
作者：
Socher, Eileen;Sticht, Heinrich
HdeA和YmgD是大肠杆菌周质中的结构同源蛋白。HdeA已被证明是一种酸活化的分子伴侣，而YmgD的功能尚未被表征。我们进行了pH滴定分子动力学模拟（pHtMD），以调查这两种蛋白质的结构变化，并评估是否YmgD也可能表现出类似的HdeA的展开行为。HdeA的解折叠途径包括部分解折叠的二聚体结构，这是随后解离的先决条件。与HdeA的耦合解折叠和解离相反，YmgD显示折叠亚基的解离，并且亚基即使在低pH值下也不经历显著的解折叠。HdeA和YmgD之间亚基稳定性的差异可以通过螺旋D的结构特征来解释，螺旋D代表HdeA中展开的起始点。总之，本研究表明YmgD要么不是酸活化的伴侣蛋白，要么至少不需要解折叠即可活化。
HdeA and YmgD are structurally homologous proteins in the periplasm of Escherichia coli. HdeA has been shown to represent an acid-activated chaperone, whereas the function of YmgD has not yet been characterized. We performed pH-titrating molecular dynamics simulations (pHtMD) to investigate the structural changes of both proteins and to assess whether YmgD may also exhibit an unfolding behavior similar to that of HdeA. The unfolding pathway of HdeA includes partially unfolded dimer structures, which represent a prerequisite for subsequent dissociation. In contrast to the coupled unfolding and dissociation of HdeA, YmgD displays dissociation of the folded subunits, and the subunits do, not undergo significant unfolding even at low pH values. The differences in subunit stability between HdeA and YmgD may be explained by the structural features of helix D, which represents the starting point of unfolding in HdeA. In summary, the present study suggests that YmgD either is not an acid-activated, chaperone or, at least, does not require unfolding for activation.