TERNARY COMPLEX OF PHE-tRNA, EF-Tu AND A GTP ANALOG. Jens Nyborg, Poul Nissen, Morten Kjeldgaard, Soren Thirup, Galina Polekhina and Brian F.C. Clark, Dept. of Molecular and Structural Biology, University of Aarhus, Langelandsgade 140, DK-8000 Aarhus C, Denmark; Ludmila Reshetnikova, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 32 Vavilov Str., 117984 Moscow, Russia

The structure of the ternary complex of yeast Phe-tRNA, T. aquaticus EF-Tu and the GTP analog GDPNP has been determined to a resolution of 2.7 Å (1). When the model of this complex is compared to the structure of EF-G:GDP (2) an unexpected macromolecular mimicry is observed. The biological implications of this mimicry will be discussed.

Elongation factors EF-Tu and EF-G catalyze the elongation step of prokaryotic protein biosynthesis. Their actions are controlled by GTP. EF-Tu:GTP forms a ternary complex with all aminoacylated tRNAs, protects the amino acid ester bond and assists in placing the cognate aminoacylated tRNA into the ribosomal A site. Inactive EF-Tu:GDP is released from the ribosome. A peptide bond is formed between the aminoacylated tRNA and the peptide on peptidyl tRNA in the P site. EF-G:GTP translocates the newly formed peptidyl tRNA into the P site and at the same time advances the mRNA one codon.

Structures of E. coli EF-Tu:GDP (3) and T. aquaticus (4) EF-Tu:GDPNP have been determined earlier. They reveal a large conformational rearrangement of domains of EF-Tu upon activation.

The structure of the ternary complex of EF-Tu shows that the tRNA is recognized in three areas. One side of the T stem helix is bound to domain 3 of EF-Tu. The 5' phosphate is recognized by conserved residues at the interface of all three domains. The 3' terminal A base is bound at a depression on domain 2 while the amino acid is found in a pocket between domains 1 and 2.

(1) P. Nissen et al., Science (1995), 270, 1464.

(2) J. Czworkowski et al., EMBO J. (1994), 13, 3661.

(3) M. Kjeldgaard and J. Nyborg, JMB (1992), 223, 721.

(4) M. Kjeldgaard et al., Structure (1993), 1, 35.