Abstract

The translational accuracy in protein synthesis is contributed to by several mechanisms in the ribosome, generally called kinetic proofreading. This process in the ribosome inhibits the non-cognate codon-anticodon interaction. However, it is not sufficient for fidelity of protein synthesis since a wrong amino acid can easily be added to the growing polypeptide chain if a tRNA while cognate to the mRNA, carries a non-cognate amino acid. Therefore, additional to the kinetic proofreading, there must be some hitherto unknown characteristic in misacylated-tRNAs to stop the process of protein synthesis if such misacylated-tRNA is accommodated in the ribosomal A-site. In order to understand this characteristic, we have performed computational quantum chemistry analysis on five different tRNA molecules, each one attached to five different amino acids with one being cognate to the tRNA and the other four non-cognate. This study shows the importance of aminoacyl-tRNA binding energy in ensuring fidelity of protein synthesis.

摘要

蛋白质合成中的翻译准确性是由核糖体中的几种机制促成的，通常称为动力学校对。核糖体中的这一过程抑制了非同源密码子-反密码子相互作用。但是，这对于蛋白质合成的保真度是不够的，因为如果与mRNA同源的tRNA携带非同源氨基酸，则很容易将错误的氨基酸添加到生长的多肽链中。因此，除了动力学校对之外，如果异酰化 tRNA 位于核糖体 A 位点，则异酰化 tRNA 中必须存在一些迄今为止未知的特征以阻止蛋白质合成过程。为了理解这一特性，我们对五种不同的 tRNA 分子进行了计算量子化学分析，每一种都与五种不同的氨基酸相连，一种与 tRNA 同源，另四种与 tRNA 无关。该研究显示了氨酰基-tRNA 结合能在确保蛋白质合成保真度方面的重要性。