Exploring the Interactome of the Queuine Salvage Protein DUF2419 in <i>Entamoeba histolytica</i>

<i>Entamoeba histolytica</i> causes amebiasis, a significant global health issue, with millions affected annually, especially in developing countries. EhDUF2419, an important protein involved in <i>E. histolytica</i>’s queuine salvage pathway and its interaction network, rema...

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Bibliographic Details
Main Authors: Jun Ye, Meirav Trebicz-Geffen, Serge Ankri
Format: Article
Language:English
Published: MDPI AG 2024-11-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/13/22/1900
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Summary:<i>Entamoeba histolytica</i> causes amebiasis, a significant global health issue, with millions affected annually, especially in developing countries. EhDUF2419, an important protein involved in <i>E. histolytica</i>’s queuine salvage pathway and its interaction network, remains unclear. To explore this, we transfected <i>E. histolytica</i> trophozoites with a plasmid encoding Myc-tagged EhDUF2419 and achieved successful overexpression. Through immunoprecipitation with the Myc antibody followed by mass spectrometry, we identified 335 proteins interacting with Myc-tagged EhDUF2419, including over 100 ribosomal proteins, along with translation initiation and elongation factors, and aminoacyl-tRNA synthetases. Ribosome purification revealed the presence of EhDUF2419 in ribosomal protein-enriched fractions. Treatment with queuosine (Q) significantly reduced the EhDUF2419 protein levels and decreased the Q-modified tRNA in Myc-tagged EhDUF2419 overexpressing trophozoites. This effect, which was Q-dependent, was not observed in strains carrying an empty vector control or overexpressing a truncated form of EhDUF2419 lacking catalytic activity. The reduction in the EhDUF2419 protein levels was regulated by proteasome-mediated degradation, as evidenced by the reduced degradation in the presence of MG132, a proteasome inhibitor. Our study uncovers the novel interaction of EhDUF2419 with ribosomal proteins and its regulation by the proteasome machinery, providing new insights into its role in <i>E. histolytica</i> and potential therapeutic strategies.
ISSN:2073-4409