Pathways & interactions
Translation elongation factor, IF5A, hypusine site (IPR019769)
Short name: Trans_elong_IF5A_hypusine_site
Translation initiation factor 5A (IF-5A) was previously reported to be involved in the first step of peptide bond formation in translation; however more recent work implicates it as a universally conserved translation elongation factor [PMID: 19424157].
eIF5A 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.
Hypusine is derived from lysine by the post-translational addition of a butylamino group (from spermidine) to the epsilon-amino group of lysine. The hypusine group is essential to the function of eIF-5A. A hypusine-containing protein has been found in archaebacteria such as Sulfolobus acidocaldarius or Methanocaldococcus jannaschii (Methanococcus jannaschii); this protein is highly similar to eIF-5A and could play a similar role in protein biosynthesis. The signature for eIF-5A is centred on the hypusine residue.
The crystal structure of IF-5A from the archaeon Pyrobaculum aerophilum has been determined to 1.75 A. 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 Escherichia coli, which has a well characterised RNA-binding fold, suggesting that IF-5A is involved in RNA binding [PMID: 9753699].
No terms assigned in this category.
- PS00302 (IF5A_HYPUSINE)