The Unique Evolutionary Distribution of Eukaryotic Elongation Factor 3

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Evolution of the Protein Synthesis Machinery and Its Regulation

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Translation, the mechanism by which proteins are synthesized based on the information encoded in mRNA, is an essential process in all living organisms. Consisting of initiation, elongation and termination phases, many aspects of this process are conserved across bacteria and eukaryotes. The elongation phase, in particular, has several well-conserved steps and universally requires two protein elongation (EF) factors. However, fungal translation elongation was determined to be unique in its absolute requirement for a third factor, the ATPase eEF3. While the exact function of eEF3 is unclear, eEF3 binds close to the E-site of the ribosome and has been proposed to facilitate the removal of deacylated tRNA from the E-site. Originally described as a “fungal-specific factor,” recent bioinformatic analysis of eEF3 distribution challenges this designation as eEF3-like proteins are found in other lower order eukaryotes. In agreement with its role as an ATPase, all the putative eEF3 homologs identified have two ABC domains. Critical residues of the two ABC domains involved in nucleotide binding and hydrolysis were highly conserved in all the putative eEF3 homologs identified, supporting the functional role of the homologs as ATPases. The HEAT and chromodomain regions, both of which have been implicated in ribosomal interactions, are less conserved than the ABC domains. Further analysis of these putative eEF3s may facilitate the elucidation of the critical functions of eEF3 in translation elongation and shed light on how the protein synthesis machinery evolved from bacteria to fungi to higher eukaryotes.


This chapter was originally published as Mateyak, M., Sasikumar, A.N., Dunaway, S., and Kinzy, T.G. (2016) The Unique Evolutionary Distribution of Eukaryotic Elongation Factor 3 in Evolution of the protein synthesis machinery and its regulation, Hernandez, G. and Jagus, R., Ed. Springer NY, NY.