<p>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 [<cite idref="PUB00046010"/>].</p><p>eIF5A is a cofactor for the Rev and Rex transactivator proteins of human immunodeficiency virus-1 and T-cell leukaemia virus I, respectively [<cite idref="PUB00000742"/>, <cite idref="PUB00003672"/>, <cite idref="PUB00010716"/>]. 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. </p><p> 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 <taxon tax_id="2285">Sulfolobus acidocaldarius</taxon> or <taxon tax_id="2190">Methanocaldococcus jannaschii</taxon> (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. </p><p>The crystal structure of IF-5A from the archaeon <taxon tax_id="13773">Pyrobaculum aerophilum</taxon> 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 <taxon tax_id="562">Escherichia coli</taxon>, which has a well characterised RNA-binding fold, suggesting that IF-5A is involved in RNA binding [<cite idref="PUB00010716"/>].</p> Translation elongation factor, IF5A, hypusine site