Energy barriers and driving forces in tRNA translocation through the ribosome

Nat Struct Mol Biol. 2013 Dec;20(12):1390-6. doi: 10.1038/nsmb.2690. Epub 2013 Nov 3.


During protein synthesis, tRNAs move from the ribosome's aminoacyl to peptidyl to exit sites. Here we investigate conformational motions during spontaneous translocation, using molecular dynamics simulations of 13 intermediate-translocation-state models obtained by combining Escherichia coli ribosome crystal structures with cryo-EM data. Resolving fast transitions between states, we find that tRNA motions govern the transition rates within the pre- and post-translocation states. Intersubunit rotations and L1-stalk motion exhibit fast intrinsic submicrosecond dynamics. The L1 stalk drives the tRNA from the peptidyl site and links intersubunit rotation to translocation. Displacement of tRNAs is controlled by 'sliding' and 'stepping' mechanisms involving conserved L16, L5 and L1 residues, thus ensuring binding to the ribosome despite large-scale tRNA movement. Our results complement structural data with a time axis, intrinsic transition rates and molecular forces, revealing correlated functional motions inaccessible by other means.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Transport
  • Cryoelectron Microscopy
  • Crystallography, X-Ray
  • Escherichia coli / genetics
  • Kinetics
  • Nucleic Acid Conformation
  • Protein Biosynthesis
  • RNA, Transfer / chemistry
  • RNA, Transfer / metabolism*
  • RNA, Transfer / physiology
  • Ribosomes / metabolism*
  • Ribosomes / physiology


  • RNA, Transfer

Associated data

  • PDB/3J4V
  • PDB/3J4W
  • PDB/3J4X
  • PDB/3J4Y
  • PDB/3J4Z
  • PDB/3J50
  • PDB/3J51
  • PDB/3J52
  • PDB/3J53
  • PDB/3J54
  • PDB/3J55
  • PDB/3J56
  • PDB/3J57
  • PDB/3J58
  • PDB/3J59
  • PDB/3J5A
  • PDB/3J5B
  • PDB/3J5C
  • PDB/3J5D
  • PDB/3J5E
  • PDB/3J5F
  • PDB/3J5G
  • PDB/3J5H
  • PDB/3J5I
  • PDB/3J5J
  • PDB/3J5K