Marín Mónica, Fernández-Calero Tamara, Ehrlich Ricardo
Biochemistry-Molecular Biology Section, Cellular and Molecular Biology Department, Faculty of Sciences, Universidad de la República, Iguá 4225, 11400, Montevideo, Uruguay.
Bioinformatics Unit, Institut Pasteur Montevideo, Mataojo 2020, 11400, Montevideo, Uruguay.
Biophys Rev. 2017 Oct;9(5):573-588. doi: 10.1007/s12551-017-0322-2. Epub 2017 Sep 24.
Polypeptides can fold into tertiary structures while they are synthesized by the ribosome. In addition to the amino acid sequence, protein folding is determined by several factors within the cell. Among others, the folding pathway of a nascent polypeptide can be affected by transient interactions with other proteins, ligands, or the ribosome, as well as by the translocation through membrane pores. Particularly, the translation machinery and the population of tRNA under different physiological or adaptive responses can dramatically affect protein folding. This review summarizes the scientific evidence describing the role of translation kinetics and tRNA populations on protein folding and addresses current efforts to better understand tRNA biology. It is organized into three main parts, which are focused on: (i) protein folding in the cellular context; (ii) tRNA biology and the complexity of the tRNA population; and (iii) available methods and technical challenges in the characterization of tRNA pools. In this manner, this work illustrates the ways by which functional properties of proteins may be modulated by cellular tRNA populations.
多肽在核糖体合成过程中就能折叠成三级结构。除氨基酸序列外，蛋白质折叠还由细胞内的多种因素决定。其中，新生多肽的折叠途径会受到与其他蛋白质、配体或核糖体的瞬时相互作用以及通过膜孔转运的影响。特别是，在不同生理或适应性反应下的翻译机制和tRNA群体能够显著影响蛋白质折叠。本综述总结了描述翻译动力学和tRNA群体对蛋白质折叠作用的科学证据，并探讨了当前为更好地理解tRNA生物学所做的努力。它分为三个主要部分，重点关注：（i）细胞环境中的蛋白质折叠；（ii）tRNA生物学和tRNA群体的复杂性；（iii）表征tRNA库的可用方法和技术挑战。通过这种方式，这项工作阐述了细胞tRNA群体调节蛋白质功能特性的方式。
