Department of LCLS Data Analytics, Linac Coherent Light Source, SLAC National Accelerator Laboratory, Menlo Park, CA 94025, USA.
Department of Mathematics, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.
Molecules. 2020 Sep 17;25(18):4262. doi: 10.3390/molecules25184262.
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.
核糖体异质性在过去几年中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了多个尺度，包括核糖体在单颗粒水平上的运动的动态方面、在细胞和亚细胞尺度上的专业化，或跨越物种的进化差异。在解决了中等至高分辨率的核糖体原子结构之后，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，我们介绍了一些最近在量化核糖体异质性方面的进展，重点是核糖体的构象和进化变化及其功能意义。这些努力强调了需要新的计算方法和比较工具，以全面模拟核糖体的连续构象转变途径及其进化。虽然开发这些方法存在一些重要的挑战，但它也为我们扩展对 cryo-EM 数据的解释和使用提供了机会，这将更广泛地有益于蛋白质和其他复合物的分子动力学和进化研究。
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