Motion of transfer RNA from the A/T state into the A-site using docking and simulations
Motion of transfer RNA from the A/T state into the A-site using docking and simulations
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DOI：
10.1002/prot.24131
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发表时间：
2012-11-01
影响因子：
2.9
通讯作者：
Devkota, Batsal
中科院分区：
文献类型：
--
作者：
Caulfield, Thomas;Devkota, Batsal
核糖体催化生长中的新生多肽链上的肽基转移反应。在这里，我们提出了一个结构机制，选择同源近同源A/T转移RNA（tRNA）。在某种程度上，翻译保真度的结构基础依赖于从近同源tRNA中过滤同源物的调节。为了研究核糖核核糖蛋白复合物中tRNA的组装，我们对整个溶剂化的70 S大肠杆菌核糖体沿着相关的辅因子、蛋白质和信使RNA（mRNA）进行了一系列全原子分子动力学（MD）模拟。我们测量了tRNA在初始结合和完全容纳之间的A/T状态的运动。对排斥反应的机理进行了研究。使用新的内部算法，我们确定了轨迹路径。尽管有很大的亚基间空腔，但可用的空间受到同样大的tRNA的限制。这篇文章描述了一个结构门，在核糖体大亚基上的螺旋71和92之间形成，限制tRNA运动。50 S核糖体的门和相互作用蛋白L14在调节过程中的两个连续子步骤中充当空间过滤器，每个子步骤需要：（1）杂交tRNA扭结中包含足够的能量和（2）密码子反密码子的沃森克里克碱基配对中包含足够的能量。我们发现，这些障碍的作用，以过滤出近同源的tRNA和促进校对的密码子反密码子。由于校对对于理解翻译的保真度至关重要，因此我们对这一过程的动态模型具有重大的生物医学意义。Proteins 2012. (c)2012 Wiley Periodicals，Inc.
The ribosome catalyzes peptidyl transfer reactions at the growing nascent polypeptide chain. Here, we present a structural mechanism for selecting cognate over near-cognate A/T transfer RNA (tRNA). In part, the structural basis for the fidelity of translation relies on accommodation to filter cognate from near-cognate tRNAs. To examine the assembly of tRNAs within the ribonucleicriboprotein complex, we conducted a series of all-atom molecular dynamics (MD) simulations of the entire solvated 70S Escherichia coli ribosome, along with its associated cofactors, proteins, and messenger RNA (mRNA). We measured the motion of the A/T state of tRNA between initial binding and full accommodation. The mechanism of rejection was investigated. Using novel in-house algorithms, we determined trajectory pathways. Despite the large intersubunit cavity, the available space is limited by the presence of the tRNA, which is equally large. This article describes a structural gate, formed between helices 71 and 92 on the ribosomal large subunit, which restricts tRNA motion. The gate and the interacting protein, L14, of the 50S ribosome act as steric filters in two consecutive substeps during accommodation, each requiring: (1) sufficient energy contained in the hybrid tRNA kink and (2) sufficient energy in the WatsonCrick base pairing of the codonanticodon. We show that these barriers act to filter out near-cognate tRNA and promote proofreading of the codonanticodon. Since proofreading is essential for understanding the fidelity of translation, our model for the dynamics of this process has substantial biomedical implications. Proteins 2012. (c) 2012 Wiley Periodicals, Inc.