Abstract
Elongation factors Tu (EF-Tu) and SelB are translational GTPases that deliver aminoacyl-tRNAs (aa-tRNAs) to the ribosome. In each canonical round of translation elongation, aa-tRNAs, assisted by EF-Tu, decode mRNA codons and insert the respective amino acid into the growing peptide chain. Stop codons usually lead to translation termination; however, in special cases UGA codons are recoded to selenocysteine (Sec) with the help of SelB. Recruitment of EF-Tu and SelB together with their respective aa-tRNAs to the ribosome is a multistep process. In this review, we summarize recent progress in understanding the role of ribosome dynamics in aa-tRNA selection. We describe the path to correct codon recognition by canonical elongator aa-tRNA and Sec-tRNASec and discuss the local and global rearrangements of the ribosome in response to correct and incorrect aa-tRNAs. We present the mechanisms of GTPase activation and GTP hydrolysis of EF-Tu and SelB and summarize what is known about the accommodation of aa-tRNA on the ribosome after its release from the elongation factor. We show how ribosome dynamics ensures high selectivity for the cognate aa-tRNA and suggest that conformational fluctuations, induced fit and kinetic discrimination play major roles in maintaining the speed and fidelity of translation.This article is part of the themed issue ‘Perspectives on the ribosome’.
Highlights
Elongation factors Tu (EF-Tu) and SelB are translational GTPases that deliver aminoacyl-tRNAs to the ribosome
We present the mechanisms of GTPase activation and GTP hydrolysis of EF-Tu and SelB and summarize what is known about the accommodation of aa-tRNA on the ribosome after its release from the elongation factor
In each round of translation elongation, mRNA triplets are decoded by aminoacyl-tRNAs which are delivered to the A site of the ribosome in the complex with elongation factor Tu (EF-Tu; in bacteria, or eEF1A in eukaryotes) and GTP
Summary
Translation of the genetic information is one of the fundamental processes in living cells. Pioneering work by Ramakrishnan and co-workers [20,21] has demonstrated how the ribosome recognizes correct codon–anticodon complexes They showed that cognate codon–anticodon base pairing induces a local conformational change in the decoding centre of the small ribosomal subunit (SSU), where two universally conserved adenines, A1492 and A1493, change their position from the ‘flipped-in’ arrangement, pointing away from the mRNA codon, towards ‘flipped-out’ oriented towards the codon– anticodon complex. Our recent reconstruction of several intermediates on the route to UGA decoding by SelB–Sec-tRNASec provides insights into the mechanism of how correct codon–anticodon recognition facilitates GTPase activation [13]. These concepts provide explanations for numerous existing observations and will stimulate new experiments and development of novel approaches to study decoding. We will summarize the current views on how the ribosome selects cognate aa-tRNA for translation
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