title: Translation elongation factor-3 (EF-3): an evolving eukaryotic ribosomal protein?
abstract: Fungi appear to be unique in their requirement for a third soluble translation elongation factor. This factor, designated elongation factor 3 (EF-3), exhibits ribosome-dependent ATPase and GTPase activities that are not intrinsic to the fungal ribosome but are nevertheless essential for translation elongation in vivo. The EF-3 polypeptide has been identified in a wide range of fungal species and the gene encoding EF-3 (YEF3) has been isolated from four fungal species (Saccharomyces cerevisiae, Candida albicans, Candida guillermondii, and Pneumocystis carinii). Computer-assisted analysis of the predicted S. cerevisiae EF-3 amino acid sequence was used to identify several potential functional domains; two ATP binding/catalytic domains conserved with equivalent domains in members of the ATP-Binding Cassette (ABC) family of proteins, an amino-terminal region showing significant similarity to the E. coli S5 ribosomal protein, and regions of predicted interaction with rRNA, tRNA, and mRNA. Furthermore, EF-3 was also found to display amino acid similarity to myosin proteins whose cellular function is to provide the motive force of muscle. The identification of these regions provides clues to both the evolution and function of EF-3. The predicted functional regions are conserved among all known fungal EF-3 proteins and a recently described homologue encoded by the Chlorella virus CVK2. We propose that EF-3 may play a role in the ribosomal optimization of the accuracy of fungal protein synthesis by altering the conformation and activity of a ribosomal "accuracy center," which is equivalent to the S4-S5-S12 ribosomal protein accuracy center domain of the E. coli ribosome. Furthermore, we suggest that EF-3 represents an evolving ribosomal protein with properties analogous to the intrinsic ATPase activities of higher eukaryotic ribosomes, which has wider implications for the evolutionary divergence of fungi from other eukaryotes.
authors.affiliation: Research School of Biosciences, University of Kent, Canterbury, United Kingdom.
authors.forename: G P
authors.initials: GP
authors.lastname: Belfield
authors.forename: N J
authors.initials: NJ
authors.lastname: Ross-Smith
authors.forename: M F
authors.initials: MF
authors.lastname: Tuite
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000235:genetics; D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000235:genetics; D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000604:Amino Acyl-tRNA Synthetases / Q000737:chemistry / Q000235:genetics; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics; D001665:Binding Sites; D005075:Biological Evolution; D004268:DNA-Binding Proteins; D004926:Escherichia coli / Q000235:genetics; D005057:Eukaryotic Cells / Q000378:metabolism*; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics*; D005658:Fungi / Q000235:genetics*; D020963:GTP Phosphohydrolase-Linked Elongation Factors / Q000737:chemistry / Q000235:genetics; D005796:Genes; D006160:Guanosine Triphosphate / Q000378:metabolism; D008969:Molecular Sequence Data; D018995:Myosin Heavy Chains / Q000737:chemistry / Q000235:genetics; D010445:Peptide Elongation Factors / Q000737:chemistry / Q000235:genetics*; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics; D017434:Protein Structure, Tertiary; D012269:Ribosomal Proteins / Q000737:chemistry / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity
chemical_list: D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D010445:Peptide Elongation Factors; D012269:Ribosomal Proteins; D029701:Saccharomyces cerevisiae Proteins; C111584:YEF3 protein, S cerevisiae; C030831:ribosomal protein S5; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D011494:Protein Kinases; D000251:Adenosine Triphosphatases; D020963:GTP Phosphohydrolase-Linked Elongation Factors; D018995:Myosin Heavy Chains; D000604:Amino Acyl-tRNA Synthetases