Trimethylamine N-oxide stabilizes RNA tertiary structure and attenuates the denaturating effects of urea
Trimethylamine N-oxide stabilizes RNA tertiary structure and attenuates the denaturating effects of urea
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DOI：
10.1021/ja0292997
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发表时间：
2003-04-16
影响因子：
15
通讯作者：
Yadav, S
中科院分区：
文献类型：
--
作者：
Gluick, TC;Yadav, S
三甲胺氮氧化物(TMAO)和尿素是渗透分子。渗透激素使细胞在恶劣或极端的环境中仍能存活。TMAO和尿素分别以大约1：2的摩尔比存在于鲨鱼和放射鱼中。在这个比例下，TMAO几乎完全抵消了尿素对蛋白质的不稳定作用。我们问，被尿素变性的RNA是否以类似于蛋白质的方式被TMAO稳定。我们发现，TMAO稳定了大肠杆菌的RN后三级结构，并以与蛋白质相同的比例抵消了尿素的变性效应。阳离子结合通常驱动RNA三级结构的形成。这些结果表明，三级结构的稳定性不仅对阳离子敏感，而且对水的组成和溶剂的性质也很敏感。我们认为三级结构折叠是由TMAO和磷酸二酯主链之间的不利相互作用驱动的。
TrimethylamineN-oxide (TMAO) and urea are osmolytes. Osmolytes allow cells to remain viable in harsh or extreme environments. Both TMAO and urea are found in shark and rays at approximate molar ratios of 1:2, respectively. At this ratio TMAO nearly completely counteracts the destabilizing effects that urea has on proteins. We ask whether RNA, which is denatured by urea, is stabilized by TMAO in a manner similar to that seen for proteins. We found that TMAO stabilizesEscherichia colitRNAfmettertiary structure and counteracts the denaturing effects of urea at the same ratios found for proteins. Cation binding usually drives RNA tertiary structure formation. These results suggest that tertiary structure stability is not only sensitive to cations but also to the aqueous composition and properties of the solvent. We propose that tertiary structure folding is driven by unfavorable interactions between TMAO and the phosphodiester backbone.