Structural Heterogeneities of the Ribosome: New Frontiers and Opportunities for Cryo-EM.

Structural Heterogeneities of the Ribosome: New Frontiers and Opportunities for Cryo-EM.
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DOI:
10.3390/molecules25184262
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发表时间:
2020-09-17
期刊:
Molecules (Basel, Switzerland)
影响因子:
--
通讯作者:
Dao Duc K
Dao Duc K
中科院分区:
其他
文献类型:
--
作者:
Poitevin F;Kushner A;Li X;Dao Duc K

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过去几年,核糖体异质性的程度引起了越来越多的关注,因为最近的研究强调了核糖体结构变异的存在。更准确地说,核糖体的异质性涵盖多个尺度,包括单颗粒水平的核糖体运动的动力学方面、细胞和亚细胞尺度的特化或物种间的进化差异。在以中高分辨率解析核糖体原子结构后,低温电子显微镜 (cryo-EM) 能够研究所有这些形式的异质性。在这篇综述中,我们介绍了量化核糖体异质性的一些最新进展,重点关注核糖体的构象和进化变异及其功能含义。这些努力凸显了对新计算方法和比较工具的需求,以全面模拟核糖体的连续构象转变途径及其进化。虽然开发这些方法提出了一些重要的挑战,但它也提供了扩展我们对冷冻电镜数据的解释和使用的机会,这将更普遍地有利于分子动力学以及蛋白质和其他复合物进化的研究。
The extent of ribosomal heterogeneity has caught increasing interest over the past few years, as recent studies have highlighted the presence of structural variations of the ribosome. More precisely, the heterogeneity of the ribosome covers multiple scales, including the dynamical aspects of ribosomal motion at the single particle level, specialization at the cellular and subcellular scale, or evolutionary differences across species. Upon solving the ribosome atomic structure at medium to high resolution, cryogenic electron microscopy (cryo-EM) has enabled investigating all these forms of heterogeneity. In this review, we present some recent advances in quantifying ribosome heterogeneity, with a focus on the conformational and evolutionary variations of the ribosome and their functional implications. These efforts highlight the need for new computational methods and comparative tools, to comprehensively model the continuous conformational transition pathways of the ribosome, as well as its evolution. While developing these methods presents some important challenges, it also provides an opportunity to extend our interpretation and usage of cryo-EM data, which would more generally benefit the study of molecular dynamics and evolution of proteins and other complexes.
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