How EF-Tu can contribute to efficient proofreading of aa-tRNA by the ribosome

Noel, Jeffrey; Whitford, Paul C.

doi:10.1038/ncomms13314

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How EF-Tu can contribute to efficient proofreading of aa-tRNA by the ribosome

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Noel, Jeffrey
Physical Chemistry, Fritz Haber Institute, Max Planck Society;
Center for Theoretical Biological Physics, Rice University;
Max Delbrück Center for Molecular Medicine, Kristallographie;

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Noel, J., & Whitford, P. C. (2016). How EF-Tu can contribute to efficient proofreading of aa-tRNA by the ribosome. Nature Communications, 7: 13314. doi:10.1038/ncomms13314.

Cite as: https://hdl.handle.net/11858/00-001M-0000-002C-16B1-5

Abstract

It has long been recognized that the thermodynamics of mRNA–tRNA base pairing is insufficient to explain the high fidelity and efficiency of aminoacyl-tRNA (aa-tRNA) selection by the ribosome. To rationalize this apparent inconsistency, Hopfield proposed that the ribosome may improve accuracy by utilizing a multi-step kinetic proofreading mechanism. While biochemical, structural and single-molecule studies have provided a detailed characterization of aa-tRNA selection, there is a limited understanding of how the physical–chemical properties of the ribosome enable proofreading. To this end, we probe the role of EF-Tu during aa-tRNA accommodation (the proofreading step) through the use of energy landscape principles, molecular dynamics simulations and kinetic models. We find that the steric composition of EF-Tu can reduce the free-energy barrier associated with the first step of accommodation: elbow accommodation. We interpret this effect within an extended kinetic model of accommodation and show how EF-Tu can contribute to efficient and accurate proofreading.