title: How EF-Tu can contribute to efficient proofreading of aa-tRNA by the ribosome.
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.
authors: Center for Theoretical Biological Physics, Rice University, Houston, Texas 77030, USA.|Max Delbrück Center for Molecular Medicine, Kristallographie, Robert-Rössle-Strasse 10, Berlin 13125, Germany.|Department of Physical Chemistry, Fritz Haber Institute of the Max Planck Society, Berlin 14195, Germany.
authors: Jeffrey K
authors: JK
authors: Noel
authors: Department of Physics, Northeastern University, Dana Research Center 111, 360 Huntington Avenue, Boston, Massachusetts 02115, USA.
authors: Paul C
authors: PC
authors: Whitford
mesh_terms: D006153:Guanosine Diphosphate / Q000737:chemistry; D007700:Kinetics; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D010444:Peptide Elongation Factor Tu / Q000378:metabolism*; D014176:Protein Biosynthesis; D011487:Protein Conformation; D012346:RNA, Transfer, Amino Acyl / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism*; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D012346:RNA, Transfer, Amino Acyl; D006153:Guanosine Diphosphate; D010444:Peptide Elongation Factor Tu