During decoding, a codon of messenger RNA is matched with its cognate aminoacyl-transfer RNA and the amino acid carried by the tRNA is added to the growing protein chain. Here we propose a molecular mechanism for the decoding phase of translation: the transorientation hypothesis. The model incorporates a newly identified tRNA binding site and utilizes a flip between two tRNA anticodon loop structures, the 5′-stacked and the 3′-stacked conformations. The anticodon loop acts as a three-dimensional hinge permitting rotation of the tRNA about a relatively fixed codon–anticodon pair. This rotation, driven by a conformational change in elongation factor Tu involving GTP hydrolysis, transorients the incoming tRNA into the A site from the D site of initial binding and decoding, where it can be proofread and accommodated. The proposed mechanisms are compatible with the known structures, conformations and functions of the ribosome and its component parts including tRNAs and EF-Tu, in both the GTP and GDP states.
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We thank D. Eisenberg and R. Dickerson for advice and for access to graphics terminals and software, A. Maris and D. Cascio for help, M. Rivera, R. Jain and J. Moore for advice, and M. Kowalczyk for the art work. This work was supported by grants to J.A.L. from the National Institutes of Health, the Astrobiology Institute, the National Science Foundation, and the Department of Energy.
The authors declare no competing financial interests.
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Simonson, A., Lake, J. The transorientation hypothesis for codon recognition during protein synthesis. Nature 416, 281–285 (2002). https://doi.org/10.1038/416281a
Reviews of Physiology, Biochemistry and Pharmacology (2005)