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

JOURNAL OF MOLECULAR BIOLOGY

卷:428

Article

Mailliot, Justine¹  de Loubresse, Nicolas Garreau¹  Yusupova, Gulnara¹  Meskauskas, Arturas²  Dinman, Jonathan D.²  Yusupov, Marat¹ 

[1] CNRS, INSERM, Inst Genet & Biol Mol & Cellulaire, UMR7104,U0964, 1 Rue Laurent Fries, F-67404 Illkirch Graffenstaden, France

[2] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA

关键词: structure;    crystallography;    uL3;    mutant;    anisomycin;   

DOI  :  10.1016/j.jmb.2016.02.013

来源: Elsevier

【 摘 要 】

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. (c) 2016 The Authors. Published by Elsevier Ltd.

【 授权许可】

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