Characterizations of the Interactions between Escherichia coil Periplasmic Chaperone HdeA and Its Native Substrates during Acid Stress
Characterizations of the Interactions between Escherichia coil Periplasmic Chaperone HdeA and Its Native Substrates during Acid Stress
复制标题
酸胁迫期间大肠杆菌周质伴侣 HdeA 与其天然底物之间相互作用的表征
DOI：
10.1021/acs.biochem.7b00724
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发表时间：
2017-10-31
期刊：
影响因子：
2.9
通讯作者：
Jin, Changwen
中科院分区：
文献类型：
--
作者：
Yu, Xing-Chi;Yang, Chengfeng;Jin, Changwen
细菌耐酸分子伴侣HdeA是一种“条件性无序”蛋白，当其经历从良好折叠的二聚体到未折叠的单体的转变时，其在低pH下起作用。二聚体解离和解折叠过程导致疏水表面的暴露，其允许与广泛的客户蛋白结合。为了充分阐明HdeA的分子伴侣机制，了解在酸胁迫期间活化的HdeA如何与其天然底物相互作用至关重要。在此，我们提出了一个核磁共振研究的pH依赖HdeA底物的相互作用。我们的研究结果表明，HdeA的激活不仅是由酸化诱导，但也受到未折叠底物的存在下。底物展开的可变程度差异调节HdeA底物相互作用，并且结合进一步影响HdeA构象。最后，我们表明，HdeA结合其基板的异质性，并讨论了HdeA基板相互作用的“两亲”模型。
The bacterial acid-resistant chaperone HdeA is a "conditionally disordered" protein that functions at low pH when it undergoes a transition from a well-folded dimer to an unfolded monomer. The dimer dissociation and unfolding processes result in exposure of hydrophobic surfaces that allows binding to a broad range of client proteins. To fully elucidate the chaperone mechanism of HdeA, it is crucial to understand how the activated HdeA interacts with its native substrates during acid stress. Herein, we present a nuclear magnetic resonance study of the pH dependent HdeA substrate interactions. Our results show that the activation of HdeA is not only induced by acidification but also regulated by the presence of unfolded substrates. The variable extent of unfolding of substrates differentially regulates the HdeA substrate interaction, and the binding further affects the HdeA conformation. Finally, we show that HdeA binds its substrates heterogeneously, and the "amphiphilic" model for HdeA substrate interaction is discussed.