Zaher Hani S, Green Rachel
Howard Hughes Medical Institute, Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Nature. 2009 Jan 8;457(7226):161-6. doi: 10.1038/nature07582. Epub 2008 Dec 17.
The overall fidelity of protein synthesis has been thought to rely on the combined accuracy of two basic processes: the aminoacylation of transfer RNAs with their cognate amino acid by the aminoacyl-tRNA synthetases, and the selection of cognate aminoacyl-tRNAs by the ribosome in cooperation with the GTPase elongation factor EF-Tu. These two processes, which together ensure the specific acceptance of a correctly charged cognate tRNA into the aminoacyl (A) site, operate before peptide bond formation. Here we report the identification of an additional mechanism that contributes to high fidelity protein synthesis after peptidyl transfer, using a well-defined in vitro bacterial translation system. In this retrospective quality control step, the incorporation of an amino acid from a non-cognate tRNA into the growing polypeptide chain leads to a general loss of specificity in the A site of the ribosome, and thus to a propagation of errors that results in abortive termination of protein synthesis.
氨酰-tRNA合成酶将转运RNA与其同源氨基酸进行氨酰化，以及核糖体与GTPase延伸因子EF-Tu协同选择同源氨酰-tRNA。这两个过程共同确保正确携带氨基酸的同源tRNA特异性进入氨酰（A）位点，在肽键形成之前起作用。在这里，我们报告了使用一个明确的体外细菌翻译系统，鉴定出一种有助于肽基转移后高保真蛋白质合成的额外机制。在这个追溯性质量控制步骤中，非同源tRNA上的氨基酸掺入到正在生长的多肽链中会导致核糖体A位点的特异性普遍丧失，从而导致错误的传播，最终导致蛋白质合成的流产性终止。
