Dataset Information

Hypusine, a polyamine-derived amino acid critical for eukaryotic translation.

ABSTRACT: The natural amino acid hypusine (N ?-4-amino-2-hydroxybutyl(lysine)) is derived from the polyamine spermidine, and occurs only in a single family of cellular proteins, eukaryotic translation factor 5A (eIF5A) isoforms. Hypusine is formed by conjugation of the aminobutyl moiety of spermidine to a specific lysine residue of this protein. The posttranslational synthesis of hypusine involves two enzymatic steps, catalyzed by deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase (DOHH). Hypusine is essential for eIF5A activity. Inactivation of either the eIF5A or the DHPS gene is lethal in yeast and mouse, underscoring the vital role of eIF5A hypusination in eukaryotic cell growth and animal development. The long and basic side chain of the hypusine residue promotes eIF5A-mediated translation elongation by facilitating peptide bond formation at polyproline stretches and at many other ribosome-pausing sites. It also enhances translation termination by stimulating peptide release. By promoting translation, the hypusine modification of eIF5A provides a key link between polyamines and cell growth regulation. eIF5A has been implicated in several human pathological conditions. Recent genetic data suggest that eIF5A haploinsufficiency or impaired deoxyhypusine synthase activity is associated with neurodevelopmental disorders in humans.

SUBMITTER: Park MH

PROVIDER: S-EPMC6290153 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Hypusine, a polyamine-derived amino acid critical for eukaryotic translation.

Park Myung Hee MH Wolff Edith C EC

The Journal of biological chemistry 20180926 48

The natural amino acid hypusine (<i>N</i><sup>ϵ</sup>-4-amino-2-hydroxybutyl(lysine)) is derived from the polyamine spermidine, and occurs only in a single family of cellular proteins, eukaryotic translation factor 5A (eIF5A) isoforms. Hypusine is formed by conjugation of the aminobutyl moiety of spermidine to a specific lysine residue of this protein. The posttranslational synthesis of hypusine involves two enzymatic steps, catalyzed by deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylas ...[more]

PMID: 30257869

Similar Datasets

Project description:Translation elongation factors facilitate protein synthesis by the ribosome. Previous studies identified two universally conserved translation elongation factors, EF-Tu in bacteria (known as eEF1A in eukaryotes) and EF-G (eEF2), which deliver aminoacyl-tRNAs to the ribosome and promote ribosomal translocation, respectively. The factor eIF5A (encoded by HYP2 and ANB1 in Saccharomyces cerevisiae), the sole protein in eukaryotes and archaea to contain the unusual amino acid hypusine (N(epsilon)-(4-amino-2-hydroxybutyl)lysine), was originally identified based on its ability to stimulate the yield (endpoint) of methionyl-puromycin synthesis-a model assay for first peptide bond synthesis thought to report on certain aspects of translation initiation. Hypusine is required for eIF5A to associate with ribosomes and to stimulate methionyl-puromycin synthesis. Because eIF5A did not stimulate earlier steps of translation initiation, and depletion of eIF5A in yeast only modestly impaired protein synthesis, it was proposed that eIF5A function was limited to stimulating synthesis of the first peptide bond or that eIF5A functioned on only a subset of cellular messenger RNAs. However, the precise cellular role of eIF5A is unknown, and the protein has also been linked to mRNA decay, including the nonsense-mediated mRNA decay pathway, and to nucleocytoplasmic transport. Here we use molecular genetic and biochemical studies to show that eIF5A promotes translation elongation. Depletion or inactivation of eIF5A in the yeast S. cerevisiae resulted in the accumulation of polysomes and an increase in ribosomal transit times. Addition of recombinant eIF5A from yeast, but not a derivative lacking hypusine, enhanced the rate of tripeptide synthesis in vitro. Moreover, inactivation of eIF5A mimicked the effects of the eEF2 inhibitor sordarin, indicating that eIF5A might function together with eEF2 to promote ribosomal translocation. Because eIF5A is a structural homologue of the bacterial protein EF-P, we propose that eIF5A/EF-P is a universally conserved translation elongation factor.

Dataset Information

Hypusine, a polyamine-derived amino acid critical for eukaryotic translation.

Publications

Hypusine, a polyamine-derived amino acid critical for eukaryotic translation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets