Dataset Information

Proteom-wide analysis of lysine N-homocysteinylation and Hcy-induced proteom changes in Saccharomyces cerevisiae

ABSTRACT: Hyperhomocysteinemia (HHcy) inhibits growth and is cytotoxic to bacterial, yeast, and mammalian cells. The aim of this study was to determine the changes in proteome of the yeast induced by HHcy and map N-homocysteinylated sites. We identified 38 up- and 32-down-regulated proteins as well as 244 N-homocysteinylation sites in 98 proteins in Saccharomyces cerevisiae; with 57 sites in 34 proteins occurring in vivo. The bioinformatics analysis indicated that the N-homocysteinylated proteins were involved in a wide range of cellular functions with mostly cytosolic and ribosomal localizations. Furthermore, we discovered that lysine N-homocysteinylation sites are surrounded by neutral, hydrophobic and buried amino acid residues, and 60% of them occur within helix. The KEGG enrichment pathway analysis of these N-Hcy-proteins suggested that N-homocysteinylation disrupts metabolism of amino acids, ribosome biogenesis and glycolysis/gluconeogenesis. These findings suggest that protein N-homocysteinylation and dysregulation of cellular proteostasis affecting ribosomal proteins, biosynthesis of amino acids and changes in basic cellular pathways signaling are involved in the toxicity of HHcy in yeast. Homologous proteins are likely to be involved in HHcy toxicity in human and animal cells. We believe that the collection of N-homocysteinylation sites presented here is an important resource for future functional studies of N-homocysteinylation in yeast.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Equus Caballus (horse) Bos Taurus (bovine) Saccharomyces Cerevisiae (baker's Yeast) Mus Musculus (mouse)

SUBMITTER: Agata Malinowska

LAB HEAD: Michal Dadlez

PROVIDER: PXD020821 | Pride | 2021-04-08

REPOSITORIES: Pride

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Publications

Proteome-Wide Analysis of Protein Lysine N-Homocysteinylation in Saccharomyces cerevisiae.

Perl A-Kaján Joanna J Malinowska Agata A Zimny Jarosl Aw JA Cysewski Dominik D Suszyńska-Zajczyk Joanna J Jakubowski Hieronim H

Journal of proteome research 20210402 5

Protein N-homocysteinylation by a homocysteine (Hcy) metabolite, Hcy-thiolactone, is an emerging post-translational modification (PTM) that occurs in all tested organisms and has been linked to human diseases. The yeast Saccharomyces cerevisiae is widely used as a model eukaryotic organism in biomedical research, including studies of protein PTMs. However, patterns of global protein N-homocysteinylation in yeast are not known. Here, we identified 68 in vivo and 197 <i ...[more]

PMID: 33797904

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Dataset Information

Proteom-wide analysis of lysine N-homocysteinylation and Hcy-induced proteom changes in Saccharomyces cerevisiae

Publications

Proteome-Wide Analysis of Protein Lysine <i>N</i>-Homocysteinylation in <i>Saccharomyces cerevisiae</i>.

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