Nature
Nature
4 years ago

Ensemble cryo-EM elucidates the mechanism of translation fidelity

Ensemble cryo-EM elucidates the mechanism of translation fidelity
Anna B. Loveland, Nikolaus Grigorieff, Andrei A. Korostelev, Gabriel Demo
Gene translation depends on accurate decoding of mRNA, the structural mechanism of which remains poorly understood. Ribosomes decode mRNA codons by selecting cognate aminoacyl-tRNAs delivered by elongation factor Tu (EF-Tu). Here we present high-resolution structural ensembles of ribosomes with cognate or near-cognate aminoacyl-tRNAs delivered by EF-Tu. Both cognate and near-cognate tRNA anticodons explore the aminoacyl-tRNA-binding site (A site) of an open 30S subunit, while inactive EF-Tu is separated from the 50S subunit. A transient conformation of decoding-centre nucleotide G530 stabilizes the cognate codon–anticodon helix, initiating step-wise ‘latching’ of the decoding centre. The resulting closure of the 30S subunit docks EF-Tu at the sarcin–ricin loop of the 50S subunit, activating EF-Tu for GTP hydrolysis and enabling accommodation of the aminoacyl-tRNA. By contrast, near-cognate complexes fail to induce the G530 latch, thus favouring open 30S pre-accommodation intermediates with inactive EF-Tu. This work reveals long-sought structural differences between the pre-accommodation of cognate and near-cognate tRNAs that elucidate the mechanism of accurate decoding.

Publisher URL: http://dx.doi.org/10.1038/nature22397

DOI: 10.1038/nature22397

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