Lysine acetylation is widespread on proteins of diverse function and localization in the protozoan parasite Toxoplasma gondii

Victoria Jeffers, William Sullivan

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

While histone proteins are the founding members of lysine acetylation substrates, it is now clear that hundreds of other proteins can be acetylated in multiple compartments of the cell. Our knowledge of the scope of this modification throughout the kingdom of life is beginning to emerge, as proteome-wide lysine acetylation has been documented in prokaryotes, Arabidopsis thaliana, Drosophila melanogaster, and human cells. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify parasite peptides enriched by immunopurification with acetyl-lysine antibody, we produced the first proteome-wide analysis of acetylation for a protozoan organism, the opportunistic apicomplexan parasite Toxoplasma gondii. The results show that lysine acetylation is abundant in the actively proliferating tachyzoite form of the parasite, which causes acute toxoplasmosis. Our approach successfully identified known acetylation marks on Toxoplasma histones and α-tubulin and detected over 400 novel acetylation sites on a wide variety of additional proteins, including those with roles in transcription, translation, metabolism, and stress responses. Importantly, an extensive set of parasite-specific proteins, including those found in organelles unique to Apicomplexa, is acetylated in the parasite. Our data provide a wealth of new information that improves our understanding of the evolution of this vital regulatory modification while potentially revealing novel therapeutic avenues. We conclude from this study that lysine acetylation was prevalent in the early stages of eukaryotic cell evolution and occurs on proteins involved in a remarkably diverse array of cellular functions, including those that are specific to parasites.

Original languageEnglish
Pages (from-to)735-742
Number of pages8
JournalEukaryotic Cell
Volume11
Issue number6
DOIs
StatePublished - Jun 2012

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Toxoplasma
Acetylation
Lysine
Parasites
Proteins
Proteome
Histones
Beginning of Human Life
Apicomplexa
Toxoplasmosis
Eukaryotic Cells
Tubulin
Tandem Mass Spectrometry
Drosophila melanogaster
Arabidopsis
Liquid Chromatography
Organelles
Peptides
Antibodies

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

Cite this

Lysine acetylation is widespread on proteins of diverse function and localization in the protozoan parasite Toxoplasma gondii. / Jeffers, Victoria; Sullivan, William.

In: Eukaryotic Cell, Vol. 11, No. 6, 06.2012, p. 735-742.

Research output: Contribution to journalArticle

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