Aminoacyl-tRNA Quality Control Provides a Speedy Solution to Discriminate Right from Wrong
Aminoacyl-tRNA Quality Control Provides a Speedy Solution to Discriminate Right from Wrong
复制标题
氨酰基-tRNA 质量控制提供快速辨别是非的解决方案
DOI：
10.1016/j.jmb.2017.10.025
复制
发表时间：
2018
影响因子：
5.6
通讯作者：
Ibba, Michael
中科院分区：
文献类型：
--
作者：
Kelly, Paul;Ibba, Michael
翻译保真度必须保持与最佳的细胞稳态高精度。虽然细胞能够容忍低水平的错误蛋白质合成，基本水平的翻译错误发生在10−4个氨基酸[1]，但错误翻译蛋白质的大量积累导致活力[2]，[3]，[4]的强烈下降。考虑到细胞质在营养利用率方面的动态和波动性质，细胞必须具备适应底物利用率快速波动的能力，否则可能会损害翻译保真度。翻译错误可能通过两种机制发生：核糖体A位点的解码错误或氨基酸与其同源trna[5]的异常配对。为了抵消tRNA氨基酰化的潜在错误，细胞进化出了负责将游离氨基酸与其同源tRNA配对的酶的校对机制，即氨基酰-tRNA合成酶（aaRSs）。为了发挥他们的作用，aars催化了一个两步过程。首先，aaRS必须从复杂的底物池中区分非同源和同源氨基酸。在同源氨基酸成功识别并与ATP配合后，形成氨酰基腺苷酸释放无机焦磷酸盐。氨基酸激活后，aaRS将氨基酸转移到其同源tRNA，在那里它可用于蛋白质合成[6]。
Translational fidelity must be maintained with a high degree of accuracy for optimal cell homeostasis. While the cell is able to tolerate low levels of erroneous protein synthesis, with basal levels of translational errors occurring 10− 4 amino acids [1], gross accumulation of mistranslated proteins leads to a strong decrease in viability [2],[3],[4]. Given the dynamic and fluctuating nature of the cytoplasm with respect to nutritional availability, the cell must be equipped to accommodate rapid fluctuations in substrate availability that might otherwise compromise translational fidelity. Translational errors can occur through two mechanisms: errors in decoding within the A site of the ribosome or aberrant pairing of amino acids with their cognate tRNAs [5]. To counteract potential errors in tRNA aminoacylation, the cell has evolved proofreading mechanisms within the enzymes responsible for pairing free amino acids with their cognate tRNAs, the aminoacyl-tRNA synthetases (aaRSs).To perform their role, aaRSs catalyze a two-step process. First, aaRS must discriminate non-cognate and cognate amino acids from a complex pool of substrates. Upon successful cognate amino acid recognition and in complex with ATP, an aminoacyl adenylate is formed releasing inorganic pyrophosphate. After amino acid activation, the aaRS transfers the amino acid to its cognate tRNA where it is available for protein synthesis [6].