Crystal Structures of the uL3 Mutant Ribosome: Illustration of the Importance of Ribosomal Proteins for Translation Efficiency.

Journal of Molecular Biology
Justine MailliotMarat Yusupov

Abstract

The ribosome has been described as a ribozyme in which ribosomal RNA is responsible for peptidyl-transferase reaction catalysis. The W255C mutation of the universally conserved ribosomal protein uL3 has diverse effects on ribosome function (e.g., increased affinities for transfer RNAs, decreased rates of peptidyl-transfer), and cells harboring this mutation are resistant to peptidyl-transferase inhibitors (e.g., anisomycin). These observations beg the question of how a single amino acid mutation may have such wide ranging consequences. Here, we report the structure of the vacant yeast uL3 W255C mutant ribosome by X-ray crystallography, showing a disruption of the A-site side of the peptidyl-transferase center (PTC). An additional X-ray crystallographic structure of the anisomycin-containing mutant ribosome shows that high concentrations of this inhibitor restore a "WT-like" configuration to this region of the PTC, providing insight into the resistance mechanism of the mutant. Globally, our data demonstrate that ribosomal protein uL3 is structurally essential to ensure an optimal and catalytically efficient organization of the PTC, highlighting the importance of proteins in the RNA-centered ribosome.

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Citations

Aug 11, 2016·Nucleic Acids Research·Rosario Francisco-VelillaEncarnación Martinez-Salas
Oct 30, 2016·Proceedings of the National Academy of Sciences of the United States of America·Zheng LiuJoachim Frank
Dec 7, 2018·Nucleic Acids Research·Sergey V MelnikovYury S Polikanov
Jun 19, 2019·International Journal of Molecular Sciences·Youri Timsit, Daniel Bennequin
Jun 4, 2020·International Journal of Molecular Sciences·Encarnacion Martinez-SalasRosario Francisco-Velilla
Jan 14, 2021·Scientific Reports·Youri TimsitDaniel Bennequin
Jun 3, 2021·International Journal of Molecular Sciences·Annalisa PecoraroAnnapina Russo
Nov 11, 2021·Microbiology and Molecular Biology Reviews : MMBR·Madhan R TirumalaiGeorge E Fox

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Methods Mentioned

BETA
X-ray

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