Mass Spectrometry Reveals the Direct Action of a Chemical Chaperone
Mass Spectrometry Reveals the Direct Action of a Chemical Chaperone
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DOI：
10.1021/acs.jpclett.8b01817
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发表时间：
2018-07-19
影响因子：
5.7
通讯作者：
Landreh，Michael
中科院分区：
文献类型：
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作者：
Gault，Joseph;Lianoudaki，Danai;Landreh，Michael
尽管化学伴侣和蛋白质之间的相互作用具有基本的生物学重要性和治疗潜力，但由于其瞬时性和非特异性性质，仍然难以捕获。使用简单的质谱分析，我们能够追踪蛋白质和化学伴侣三甲胺-N-氧化物 (TMAO) 之间的相互作用。通过这种方式，我们直接观察到TMAO和变性尿素的抵消作用是由TMAO从蛋白质表面排除而驱动的，而表面活性剂月桂基二甲胺-N-氧化物不能被取代。我们的结果清楚地证明了 TMAO 的直接陪伴机制，证实了广泛的计算研究，并为使用非变性质谱和相关技术研究分子细节中的化学伴侣铺平了道路。
Despite their fundamental biological importance and therapeutic potential, the interactions between chemical chaperones and proteins remain difficult to capture due to their transient and nonspecific nature. Using a simple mass spectrometric assay, we are able to follow the interactions between proteins and the chemical chaperone trimethylamine-N-oxide (TMAO). In this manner, we directly observe that the counteraction of TMAO and the denaturant urea is driven by the exclusion of TMAO from the protein surface, whereas the surfactant lauryl dimethylamine-N-oxide cannot be displaced. Our results clearly demonstrate a direct chaperoning mechanism for TMAO, corroborating extensive computational studies, and pave the way for the use of nondenaturing mass spectrometry and related techniques to study chemical chaperones in molecular detail.