The Conformational Change in Elongation Factor Tu Involves Separation of Its Domains,Biochemistry

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The Conformational Change in Elongation Factor Tu Involves Separation of Its Domains
Biochemistry ( IF 2.9 ) Pub Date : 2017-10-27 00:00:00 , DOI: 10.1021/acs.biochem.7b00591
Jonathan Lai ₁ , Zhaleh Ghaemi ₁ , Zaida Luthey-Schulten _{1,

2,

3,

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Affiliation

Elongation factor Tu (EF-Tu) is a highly conserved GTPase that is responsible for supplying the aminoacylated tRNA to the ribosome. Upon binding to the ribosome, EF-Tu undergoes GTP hydrolysis, which drives a major conformational change, triggering the release of aminoacylated tRNA to the ribosome. Using a combination of molecular simulation techniques, we studied the transition between the pre- and post-hydrolysis structures through two distinct pathways. We show that the transition free energy is minimal along a non-intuitive pathway that involves “separation” of the GTP binding domain (domain 1) from the OB folds (domains 2 and 3), followed by domain 1 rotation, and, eventually, locking the EF-Tu conformation in the post-hydrolysis state. The domain separation also leads to a slight extension of the linker connecting domain 1 to domain 2. Using docking tools and correlation-based analysis, we identified and characterized the EF-Tu conformations that release the tRNA. These calculations suggest that EF-Tu can release the tRNA before the domains separate and after domain 1 rotates by 25°. We also examined the EF-Tu conformations in the context of the ribosome. Given the high degrees of sequence similarity with other translational GTPases, we predict a similar separation mechanism is followed.

中文翻译：

延伸因子Tu的构象变化涉及其域的分离

延伸因子Tu（EF-Tu）是高度保守的GTPase，负责向核糖体供应氨基酰化的tRNA。与核糖体结合后，EF-Tu进行GTP水解，从而驱动主要的构象变化，从而触发氨基酰化的tRNA向核糖体的释放。使用分子模拟技术的组合，我们通过两个不同的途径研究了水解前和水解后结构之间的过渡。我们显示，沿着涉及到GTP结合域（域1）与OB折叠（域2和3）“分离”的非直觉途径，过渡自由能极小，随后域1旋转，最终，将EF-Tu构象锁定在水解后状态。域的分离还导致将域1连接到域2的链接程序的轻微扩展。使用对接工具和基于相关性的分析，我们鉴定并表征了释放tRNA的EF-Tu构象。这些计算表明，EF-Tu可以在结构域分离之前和结构域1旋转25°之后释放tRNA。我们还检查了核糖体背景下的EF-Tu构象。鉴于与其他翻译GTP酶的高度序列相似性，我们预测将遵循类似的分离机制。

更新日期：2017-10-28

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