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Title: Differences in the path to exit the ribosome across the three domains of life

Journal Article · · Nucleic Acids Research
DOI: https://doi.org/10.1093/nar/gkz106 · OSTI ID:1625576
 [1];  [2];  [3];  [4];  [5]
  1. Computer Science Division, University of California, Berkeley, CA 94720, USA; DOE/OSTI
  2. Computer Science Division, University of California, Berkeley, CA 94720, USA
  3. Department of Mathematics, University of California, Berkeley, CA 94720, USA
  4. Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA; Department of Chemistry, University of California, Berkeley, CA 94720, USA; Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA
  5. Computer Science Division, University of California, Berkeley, CA 94720, USA; Department of Statistics, University of California, Berkeley, CA 94720, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA

The ribosome exit tunnel is an important structure involved in the regulation of translation and other essential functions such as protein folding. By comparing 20 recently obtained cryo-EM and X-ray crystallography structures of the ribosome from all three domains of life, we here characterize the key similarities and differences of the tunnel across species. We first show that a hierarchical clustering of tunnel shapes closely reflects the species phylogeny. Then, by analyzing the ribosomal RNAs and proteins, we explain the observed geometric variations and show direct association between the conservations of the geometry, structure and sequence. We find that the tunnel is more conserved in the upper part close to the polypeptide transferase center, while in the lower part, it is substantially narrower in eukaryotes than in bacteria. Furthermore, we provide evidence for the existence of a second constriction site in eukaryotic exit tunnels. Overall, these results have several evolutionary and functional implications, which explain certain differences between eukaryotes and prokaryotes in their translation mechanisms. In particular, they suggest that major co-translational functions of bacterial tunnels were externalized in eukaryotes, while reducing the tunnel size provided some other advantages, such as facilitating the nascent chain elongation and enabling antibiotic resistance.

Research Organization:
Lawrence Berkeley National Lab (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
Chan Zuckerburg Biohub; National Institutes of Health (NIH); Packard Fellowship; USDOE Office of Science (SC)
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
1625576
Journal Information:
Nucleic Acids Research, Journal Name: Nucleic Acids Research Journal Issue: 8 Vol. 47; ISSN 0305-1048
Publisher:
Oxford University PressCopyright Statement
Country of Publication:
United States
Language:
English

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Protein Folding at the Exit Tunnel journal June 2011
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A comparative study of ribosomal proteins: linkage between amino acid distribution and ribosomal assembly journal January 2013
Universal and domain-specific sequences in 23S–28S ribosomal RNA identified by computational phylogenetics journal August 2015
Non-Bulk-Like Solvent Behavior in the Ribosome Exit Tunnel journal October 2010
CAVER 3.0: A Tool for the Analysis of Transport Pathways in Dynamic Protein Structures journal October 2012
The impact of ribosomal interference, codon usage, and exit tunnel interactions on translation elongation rate variation journal January 2018
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Finding and Characterizing Tunnels in Macromolecules with Application to Ion Channels and Pores journal January 2009
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Translational Control by Ribosome Pausing in Bacteria: How a Non-uniform Pace of Translation Affects Protein Production and Folding journal January 2021
Structural Heterogeneities of the Ribosome: New Frontiers and Opportunities for Cryo-EM journal September 2020
Cotranslational Folding of Proteins on the Ribosome journal January 2020