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[密码子冗余在共翻译蛋白质折叠决定中的作用]

[Role of the code redundancy in determining cotranslational protein folding].

作者信息

Krasheninnikov I A, Komar A A, Adzhubeĭ I A

出版信息

Biokhimiia. 1989 Feb;54(2):187-200.

PMID:2742922
Abstract

It has been demonstrated earlier in our laboratory that rare codon clusters can determine the boundaries of the polypeptide chain fragments of the same secondary structure type during the co-translational protein folding. According to this data, co-translational protein folding can occur under condition of a correlation between the frequency of codon choice in mRNAs and the relative abundance of their isoaccepting tRNAs. The alterations in the spectrum and concentrations of the isoaccepting tRNAs in different cells were demonstrated by many authors. The existence of a mechanism of the coordinate regulation of the levels (activities) of the isoaccepting tRNAs, corresponding aminoacyl-tRNA synthetases and mRNAs predominantly translated at a given moment of time can be suggested. Such a mechanism can ensure the needed accuracy of the protein folding process. Analysis of gene sequences of various pro- and eukaryotic organisms carried out in the present work revealed that the codon usage frequency spectra of simultaneously synthesized proteins are similar. The relative appearance of the most rare and frequent codons in investigated gene sequences displays a high degree of conservatism. It has also been found that structural-homologous proteins from different organisms (cytochromes c, myoglobins) have very similar codon frequency distribution profiles. This property retains despite the significant variations in the codon usage spectra in the investigated gene sequences. The data obtained indicate that the codon distribution in mRNAs whose diversity is mainly conditioned by the genetic code redundance is a program that determines translational rates of different mRNA parts thus controlling the spatial folding of the synthesized peptide chain.

摘要

我们实验室之前已经证明,在共翻译蛋白质折叠过程中,稀有密码子簇可以决定相同二级结构类型的多肽链片段的边界。根据这些数据,共翻译蛋白质折叠可以在mRNA中密码子选择频率与其同工受体tRNA相对丰度之间存在相关性的条件下发生。许多作者都证明了不同细胞中同工受体tRNA的谱和浓度会发生变化。可以推测存在一种对同工受体tRNA、相应的氨酰tRNA合成酶和在特定时刻主要翻译的mRNA的水平(活性)进行协调调节的机制。这样一种机制可以确保蛋白质折叠过程所需的准确性。在本研究中对各种原核和真核生物的基因序列进行分析发现,同时合成的蛋白质的密码子使用频率谱是相似的。在所研究的基因序列中,最稀有和最频繁密码子的相对出现显示出高度的保守性。还发现来自不同生物体的结构同源蛋白(细胞色素c、肌红蛋白)具有非常相似的密码子频率分布谱。尽管在所研究的基因序列中密码子使用谱存在显著差异,但这一特性仍然保留。所获得的数据表明,mRNA中的密码子分布是一个程序,其多样性主要由遗传密码冗余决定,该程序决定了不同mRNA部分的翻译速率,从而控制合成肽链的空间折叠。

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