Folding at the rhythm of the rare codon beat
Folding at the rhythm of the rare codon beat
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DOI：
10.1002/biot.200800089
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发表时间：
2008-08-01
影响因子：
4.7
通讯作者：
Marin, Monica
中科院分区：
文献类型：
--
作者：
Marin, Monica
在异源系统中以高水平生产蛋白质的持续困难，以及无法理解与蛋白质聚集相关的病理，突出了我们对体内蛋白质折叠机制的有限知识。提高重组蛋白的产量和质量的尝试是多种多样的，通常涉及优化细胞生长温度、使用同义密码子和/或共表达tRNA、分子伴侣和折叠催化剂等。虽然蛋白质的二级结构可以在很大程度上由氨基酸序列决定，但细胞内的蛋白质折叠受到氨基酸序列以外的一系列因素的影响。新生多肽的折叠途径可以受到与其他蛋白质和配体、核糖体的瞬时相互作用、穿过孔膜的易位、氧化还原条件等的影响。翻译速率以及翻译机制本身可以显著影响蛋白质折叠，从而影响蛋白质产物的结构和功能。本文综述了目前的努力，以更好地了解如何使用同义密码子的mRNA和tRNA的可用性可以调节翻译动力学，影响折叠，结构和蛋白质的生物活性。
The persistent difficulties in the production of protein at high levels in heterologous systems, as well as the inability to understand pathologies associated with protein aggregation, highlight our limited knowledge on the mechanisms of protein folding in vivo. Attempts to improve yield and quality of recombinant proteins are diverse, frequently involving optimization of the cell growth temperature, the use of synonymous codons and/or the co-expression of tRNAs, chaperones and folding catalysts among others. Although protein secondary structure can be determined largely by the amino acid sequence, protein folding within the cell is affected by a range of factors beyond amino acid sequence. The folding pathway of a nascent polypeptide can be affected by transient interactions with other proteins and ligands, the ribosome, translocation through a pore membrane, redox conditions, among others. The translation rate as well as the translation machinery itself can dramatically affect protein folding, and thus the structure and function of the protein product. This review addresses current efforts to better understand how the use of synonymous codons in the mRNA and the availability of tRNAs can modulate translation kinetics, affecting the folding, the structure and the biological activity of proteins.