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Anisotropic fluctuations in the ribosome determine tRNA kinetics

Authors

  • H. Yang
  • J.K. Noel
  • P.C. Whitford

Journal

  • Journal of Physical Chemistry B

Citation

  • J Phys Chem B 121 (47): 10593-10601

Abstract

  • The ribosome is a large ribonucleoprotein complex that is responsible for the production of proteins in all organisms. Accommodation is the process by which an incoming aminoacyl-tRNA (aa-tRNA) molecule binds the ribosomal A site, and its kinetics has been implicated in the accuracy of tRNA selection. In addition to rearrangements in the aa-tRNA molecule, the L11 stalk can undergo large-scale anisotropic motions during translation. To explore the potential impact of this protruding region on the rate of aa-tRNA accommodation, we used molecular dynamics simulations with a simplified model to evaluate the free energy as a function of aa-tRNA position. Specifically, these calculations describe the transition between A/T and elbow-accommodated (EA) configurations (~20 {Angstrom} displacement). We find that the free-energy barrier associated with elbow accommodation is proportional to the degree of mobility exhibited by the L11 stalk. That is, when L11 is more rigid, the free-energy barrier height is decreased. This effect arises from the ability of L11 to confine, and thereby destabilize, the A/T ensemble. In addition, when elongation factor Tu (EF-Tu) is present, the A/T ensemble is further destabilized in an L11-dependent manner. These results provide a framework that suggests how next-generation experiments may precisely control the dynamics of the ribosome.


DOI

doi:10.1021/acs.jpcb.7b06828