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Flipping of the Ribosomal A-Site Adenines Provides a Basis for tRNA Selection

机译:核糖体A位腺嘌呤的翻转提供了tRNA选择的基础

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Ribosomes control the missense error rate of -10~(-4) during translation though quantitative contributions of individual mechanistic steps of the conformational changes yet to be fully determined. Biochemical and biophysical studies led to a qualitative tRNA selection model in which ribosomal A-site residues A1492 and A1493 (A1492/3) flip out in response to cognate tRNA binding, promoting the subsequent reactions, but not in the case of near-cognate or non-cognate tRNA. However, this model was recently questioned by X-ray structures revealing conformations of extraheli-cal A1492/3 and domain closure of the decoding center in both cognate and near-cognate tRNA bound ribo-some complexes, suggesting that the non-specific flipping of A1492/3 has no active role in tRNA selection. We explore this question by carrying out molecular dynamics simulations, aided with fluorescence and NMR experiments, to probe the free energy cost of extrahelical flipping of 1492/3 and the strain energy associated with domain conformational change.
机译:核糖体控制翻译过程中的错义错误率在-10〜(-4),尽管构象变化的各个机械步骤的定量贡献尚未完全确定。生化和生物物理研究导致了定性的tRNA选择模型,其中核糖体A位残基A1492和A1493(A1492 / 3)响应相关的tRNA结合而翻转,促进了后续反应,但对于近同源或非同源的情况则不然非同源tRNA。然而,该模型最近受到X射线结构的质疑,该结构揭示了同源和近同源tRNA结合的核糖体复合物中的hehelical A1492 / 3构象和解码中心的域关闭,这表明核糖体复合物的非特异性翻转A1492 / 3在tRNA选择中不起作用。我们通过进行分子动力学模拟,并借助荧光和NMR实验探索这个问题,以探究1492/3螺旋外翻转的自由能成本以及与结构域构象变化相关的应变能。

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