Structural dynamics of translation elongation factor Tu during aa-tRNA delivery to the ribosome

Nucleic Acids Res. 2018 Sep 19;46(16):8651-8661. doi: 10.1093/nar/gky651.

Abstract

The GTPase elongation factor EF-Tu delivers aminoacyl-tRNAs to the mRNA-programmed ribosome during translation. Cognate codon-anticodon interaction stimulates GTP hydrolysis within EF-Tu. It has been proposed that EF-Tu undergoes a large conformational change subsequent to GTP hydrolysis, which results in the accommodation of aminoacyl-tRNA into the ribosomal A-site. However, this proposal has never been tested directly. Here, we apply single-molecule total internal reflection fluorescence microscopy to study the conformational dynamics of EF-Tu when bound to the ribosome. Our studies show that GTP hydrolysis initiates a partial, comparatively small conformational change of EF-Tu on the ribosome, not directly along the path from the solution 'GTP' to the 'GDP' structure. The final motion is completed either concomitant with or following dissociation of EF-Tu from the ribosome. The structural transition of EF-Tu on the ribosome is slower when aa-tRNA binds to a cognate versus a near-cognate codon. The resulting longer residence time of EF-Tu on the ribosome may be important for promoting accommodation of the cognate aminoacyl-tRNA into the A-site.

Publication types

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

MeSH terms

  • Anticodon / genetics
  • Codon / genetics
  • Escherichia coli / genetics
  • GTP Phosphohydrolases / chemistry*
  • GTP Phosphohydrolases / genetics
  • Guanosine Diphosphate / chemistry
  • Guanosine Triphosphate / chemistry
  • Hydrolysis
  • Kinetics
  • Peptide Elongation Factor Tu / chemistry*
  • Peptide Elongation Factor Tu / genetics
  • Protein Biosynthesis / genetics
  • Protein Conformation
  • RNA, Messenger / chemistry
  • RNA, Messenger / genetics
  • RNA, Transfer, Amino Acyl / chemistry
  • RNA, Transfer, Amino Acyl / genetics*
  • Ribosomes / chemistry
  • Ribosomes / genetics*

Substances

  • Anticodon
  • Codon
  • RNA, Messenger
  • RNA, Transfer, Amino Acyl
  • Guanosine Diphosphate
  • Guanosine Triphosphate
  • GTP Phosphohydrolases
  • Peptide Elongation Factor Tu