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Proteins. 2012 Nov;80(11):2489-500. doi: 10.1002/prot.24131. Epub 2012 Jul 28.

Motion of transfer RNA from the A/T state into the A-site using docking and simulations.

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  • 1School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332, USA.


The ribosome catalyzes peptidyl transfer reactions at the growing nascent polypeptide chain. Here, we present a structural mechanism for selecting cognate over near-cognate A/T transfer RNA (tRNA). In part, the structural basis for the fidelity of translation relies on accommodation to filter cognate from near-cognate tRNAs. To examine the assembly of tRNAs within the ribonucleic-riboprotein complex, we conducted a series of all-atom molecular dynamics (MD) simulations of the entire solvated 70S Escherichia coli ribosome, along with its associated cofactors, proteins, and messenger RNA (mRNA). We measured the motion of the A/T state of tRNA between initial binding and full accommodation. The mechanism of rejection was investigated. Using novel in-house algorithms, we determined trajectory pathways. Despite the large intersubunit cavity, the available space is limited by the presence of the tRNA, which is equally large. This article describes a "structural gate," formed between helices 71 and 92 on the ribosomal large subunit, which restricts tRNA motion. The gate and the interacting protein, L14, of the 50S ribosome act as steric filters in two consecutive substeps during accommodation, each requiring: (1) sufficient energy contained in the hybrid tRNA kink and (2) sufficient energy in the Watson-Crick base pairing of the codon-anticodon. We show that these barriers act to filter out near-cognate tRNA and promote proofreading of the codon-anticodon. Since proofreading is essential for understanding the fidelity of translation, our model for the dynamics of this process has substantial biomedical implications.

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