Head swivel on the ribosome facilitates translocation by means of intra-subunit tRNA hybrid sites

Nature. 2010 Dec 2;468(7324):713-6. doi: 10.1038/nature09547.


The elongation cycle of protein synthesis involves the delivery of aminoacyl-transfer RNAs to the aminoacyl-tRNA-binding site (A site) of the ribosome, followed by peptide-bond formation and translocation of the tRNAs through the ribosome to reopen the A site. The translocation reaction is catalysed by elongation factor G (EF-G) in a GTP-dependent manner. Despite the availability of structures of various EF-G-ribosome complexes, the precise mechanism by which tRNAs move through the ribosome still remains unclear. Here we use multiparticle cryoelectron microscopy analysis to resolve two previously unseen subpopulations within Thermus thermophilus EF-G-ribosome complexes at subnanometre resolution, one of them with a partly translocated tRNA. Comparison of these substates reveals that translocation of tRNA on the 30S subunit parallels the swivelling of the 30S head and is coupled to unratcheting of the 30S body. Because the tRNA maintains contact with the peptidyl-tRNA-binding site (P site) on the 30S head and simultaneously establishes interaction with the exit site (E site) on the 30S platform, a novel intra-subunit 'pe/E' hybrid state is formed. This state is stabilized by domain IV of EF-G, which interacts with the swivelled 30S-head conformation. These findings provide direct structural and mechanistic insight into the 'missing link' in terms of tRNA intermediates involved in the universally conserved translocation process.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Binding Sites
  • Cryoelectron Microscopy
  • Crystallography, X-Ray
  • Guanosine Diphosphate / chemistry
  • Guanosine Diphosphate / metabolism
  • Models, Molecular
  • Movement*
  • Peptide Elongation Factor G / chemistry
  • Peptide Elongation Factor G / metabolism
  • Protein Biosynthesis
  • Protein Conformation
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism
  • RNA, Transfer / chemistry
  • RNA, Transfer / metabolism*
  • RNA, Transfer / ultrastructure
  • Ribosome Subunits, Small, Bacterial / chemistry*
  • Ribosome Subunits, Small, Bacterial / metabolism*
  • Ribosome Subunits, Small, Bacterial / ultrastructure
  • Thermus thermophilus / chemistry


  • Peptide Elongation Factor G
  • Protein Subunits
  • Guanosine Diphosphate
  • RNA, Transfer

Associated data

  • PDB/2XSY
  • PDB/2XTG
  • PDB/2XUX
  • PDB/2XUY