Crystal structure of elongation factor 4 bound to a clockwise ratcheted ribosome

Science. 2014 Aug 8;345(6197):684-7. doi: 10.1126/science.1253525.

Abstract

Elongation factor 4 (EF4/LepA) is a highly conserved guanosine triphosphatase translation factor. It was shown to promote back-translocation of tRNAs on posttranslocational ribosome complexes and to compete with elongation factor G for interaction with pretranslocational ribosomes, inhibiting the elongation phase of protein synthesis. Here, we report a crystal structure of EF4-guanosine diphosphate bound to the Thermus thermophilus ribosome with a P-site tRNA at 2.9 angstroms resolution. The C-terminal domain of EF4 reaches into the peptidyl transferase center and interacts with the acceptor stem of the peptidyl-tRNA in the P site. The ribosome is in an unusual state of ratcheting with the 30S subunit rotated clockwise relative to the 50S subunit, resulting in a remodeled decoding center. The structure is consistent with EF4 functioning either as a back-translocase or a ribosome sequester.

Publication types

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

MeSH terms

  • Crystallography, X-Ray
  • Escherichia coli Proteins / chemistry*
  • Nucleic Acid Conformation
  • Peptide Initiation Factors
  • Protein Structure, Tertiary
  • RNA, Transfer / chemistry
  • Ribosome Subunits, Small, Bacterial / chemistry*
  • Thermus thermophilus
  • Transcriptional Elongation Factors / chemistry*

Substances

  • Escherichia coli Proteins
  • LepA protein, E coli
  • Peptide Initiation Factors
  • Transcriptional Elongation Factors
  • RNA, Transfer

Associated data

  • PDB/4QJS
  • PDB/4QJT