Hypusination

Hypusination is a post-translational modification that occurs on a specific arginine residue within the eukaryotic translation initiation factor 5A (eIF5A). This modification is unique and essential for the function of eIF5A, which plays a critical role in protein synthesis. The process involves the addition of a hypusine residue, which is N6-(4-amino-2-hydroxybutyl)lysine, to a lysine in eIF5A. This occurs in two steps. The first step is the deoxyhypusination of a specific lysine residue by a deoxyhypusine synthase enzyme, which transfers a 4-aminobutyl moiety from spermidine. The second step is the hydroxylation of the deoxyhypusine residue by a deoxyhypusine hydroxylase enzyme, forming the mature hypusine modification.

The hypusination of eIF5A is crucial for its ability to promote the elongation of translation, particularly for mRNAs containing proline codons, which are often challenging for the ribosome to process. Hypusinated eIF5A is thought to help stabilize the ribosome during these difficult steps, preventing frameshifting and ensuring accurate protein synthesis. The modification is highly conserved across eukaryotes, highlighting its fundamental importance. Dysregulation of hypusination has been linked to various cellular processes and diseases, suggesting that this modification is a significant regulatory point in gene expression. Research into hypusination continues to uncover its intricate roles in cellular life and disease.