Pathways & interactions
Translation elongation factor IF5A, archaeal (IPR022847)
Short name: Transl_elong_IF5A_arc
Overlapping homologous superfamilies
- Translation elongation factor IF5A-like (IPR001884)
- Translation elongation factor IF5A, archaeal (IPR022847)
Eukaryotic eIF-5A was initially thought to function as a translation initiation factor, based on its ability to stimulate methionyl-puromycin synthesis. However, subsequent work revealed a role for eIF5A in translation elongation [PMID: 19424157, PMID: 28392174]. Depletion or inactivation of eIF-5A in the yeast Saccharomyces cerevisiae (Baker's yeast) resulted in the accumulation of polysomes and an increase in ribosomal transit times. Addition of recombinant eIF-5A from yeast, but not a derivative lacking hypusine, enhanced the rate of tripeptide synthesis in vitro. Moreover, inactivation of eIF-5A mimicked the effects of the eEF2 inhibitor sordarin, indicating that eIF-5A might function together with eEF2 to promote ribosomal translocation. Finally, it was shown that eIF5A is specifically required to promote peptide-bond formation between consecutive proline residues. It has been proposed to stimulate the peptidyl-transferase activity of the ribosome and facilitate the reactivity of poor substrates like proline [PMID: 23727016].
eIF-5A is a cofactor for the Rev and Rex transactivator proteins of human immunodeficiency virus-1 and T-cell leukaemia virus I, respectively [PMID: 8347280, PMID: 1903841, PMID: 9753699]. IF-5A is the sole protein in eukaryotes and archaea to contain the unusual amino acid hypusine (Ne-(4-amino-2-hydroxybutyl)lysine) that is an absolute functional requirement. The first step in the post-translational modification of lysine to hypusine is catalyzed by the enzyme deoxyhypusine synthase, the structure of which has been reported [PMID: 9493264].
The archaeal IF-5A proteins have not been studied as comprehensively as their eukaryotic homologues, though the crystal structure of the Pyrobaculum aerophilum protein has been determined. Unmodified P. aerophilum IF-5A is found to be a beta structure with two domains and three separate hydrophobic cores. The lysine (Lys42) that is post-translationally modified by deoxyhypusine synthase is found at one end of the IF-5A molecule in a turn between beta strands beta4 and beta5; this lysine residue is freely solvent accessible. The C-terminal domain is found to be homologous to the cold-shock protein CspA of E. coli, which has a well characterised RNA-binding fold, suggesting that IF-5A is involved in RNA binding [PMID: 9753699].
This entry represents the archaeal IF-5A proteins.
- MF_00085 (eIF_5A)