Structural Heterogeneities of the Ribosome: New Frontiers and Opportunities for Cryo-EM
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
Department of Computer Science, University of British Columbia, Vancouver, BC V6T 1Z4, Canada
Department of Zoology, University of British Columbia, Vancouver, BC V6T 1Z4, Canada
Author to whom correspondence should be addressed.
Academic Editor: Quentin Vicens
Molecules 2020, 25(18), 4262; https://doi.org/10.3390/molecules25184262
Received: 25 August 2020 / Revised: 11 September 2020 / Accepted: 15 September 2020 / Published: 17 September 2020
(This article belongs to the Special Issue Frontiers in RNA Structure)
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.