Global profiling of lysine 2-hydroxyisobutyrylome in Toxoplasma gondii using affinity purification mass spectrometry
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GENETICS, EVOLUTION, AND PHYLOGENY - ORIGINAL PAPER
Global profiling of lysine 2-hydroxyisobutyrylome in Toxoplasma gondii using affinity purification mass spectrometry Lan-Bi Nie 1,2 & Qin-Li Liang 2 & Hany M. Elsheikha 3 & Rui Du 1 & Xing-Quan Zhu 2,4
&
Fa-Cai Li 2,5
Received: 5 August 2020 / Accepted: 6 October 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Lysine 2-hydroxyisobutyrylation (Khib) is a recently discovered and evolutionarily conserved form of protein post-translational modification (PTM) found in mammalian and yeast cells. Previous studies have shown that Khib plays roles in the activity of gene transcription and Khib-containing proteins are closely related to the cellular metabolism. In this study, a global Khib-containing analysis using the latest databases (ToxoDB 46, 8322 sequences, downloaded on April 16, 2020) and sensitive immune-affinity enrichment coupled with liquid chromatography-tandem mass spectrometry was performed. A total of 1078 Khib modification sites across 400 Khib-containing proteins were identified in tachyzoites of Toxoplasma gondii RH strain. Bioinformatics and functional enrichment analysis showed that Khib-modified proteins were associated with various biological processes, such as ribosome, glycolysis/gluconeogenesis, and central carbon metabolism. Interestingly, many proteins of the secretory organelles (e.g., microneme, rhoptry, and dense granule) that play roles in the infection cycle of T. gondii were found to be Khib-modified, suggesting the involvement of Khib in key biological process during T. gondii infection. We also found that histone proteins, key enzymes related to cellular metabolism, and several glideosome components had Khib sites. These results expanded our understanding of the roles of Khib in T. gondii and should promote further investigations of how Khib regulates gene expression and key biological functions in T. gondii. Keywords Toxoplasma gondii . Post-translational modification (PTM) . Lysine 2-hydroxyisobutyrylation . Tachyzoite
Introduction Toxoplasma gondii is an obligate intracellular apicomplexan protozoan which has a worldwide distribution in humans and animals (Montoya and Liesenfeld 2004). Infection by this parasite can cause encephalitis and retinitis, and even death particularly in immunocompromised individuals (Elsheikha
2008). T. gondii exists in three main developmental forms, namely tachyzoites, bradyzoites, and sporozoites (Lindsay et al. 1991). Tachyzoites are responsible for the lytic cycle of invasion, replication, and egress of the host cells, leading to acute toxoplasmosis (Dubey et al. 2009). T. gondii has received global attention because of some of its unusual biological, epidemiological, and clinical features, including
Handling Editor: Una Ryan * Xing-Quan Zhu [email protected]
2
State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzh
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