Academic Journal
Molecular characterisation of Toxoplasma gondii Mre11 reveals unique structural features and potential as a therapeutic target.
| Τίτλος: | Molecular characterisation of Toxoplasma gondii Mre11 reveals unique structural features and potential as a therapeutic target. |
|---|---|
| Συγγραφείς: | Ruiz DM; Instituto de Ciencia y Tecnología de Alimentos y Ambiente (INCITAA), Comisión de Investigaciones Científicas de la Provincia de Buenos Aires (CIC) - Universidad Nacional de Mar del Plata (UNMdP), Mar del Plata, Argentina. dmruiz@mdp.edu.ar., Turowski VR; Instituto de Investigaciones Biológicas (IIB), Consejo Nacional de Investigaciones Científicas (CONICET) - Universidad Nacional de Mar del Plata (UNMdP), Mar del Plata, Argentina. vturowski@mdp.edu.ar., Sullivan WJ Jr; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA., Angel SO; Instituto Tecnológico de Chascomús (CONICET-UNSAM), Chascomús, Provincia de Buenos Aires, Argentina.; Escuela de Bio y Nanotecnologías (UNSAM), San Martín, Argentina. |
| Πηγή: | Scientific reports [Sci Rep] 2025 Dec 17; Vol. 15 (1), pp. 43994. Date of Electronic Publication: 2025 Dec 17. |
| Τύπος έκδοσης: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: London : Nature Publishing Group, copyright 2011- |
| Ιατρικοί όροι (MeSH): | Toxoplasma*/enzymology , Toxoplasma*/genetics , Protozoan Proteins*/chemistry , Protozoan Proteins*/metabolism , Protozoan Proteins*/genetics , MRE11 Homologue Protein*/chemistry , MRE11 Homologue Protein*/metabolism , MRE11 Homologue Protein*/genetics, Humans ; DNA Repair ; Models, Molecular ; Amino Acid Sequence |
| Περίληψη: | The Mre11 enzyme plays a central role in essential cellular processes such as DNA repair and meiosis, where its endonuclease and exonuclease activities are critical for maintaining genomic stability. Previous studies have linked Mre11 to cell cycle regulation and cancer progression; however, knowledge about DNA processing mechanisms in medically relevant protozoan parasites remains limited. Toxoplasma gondii harbours several essential genes, involved in the DNA damage response, including mre11. The aim of this study was to characterize T. gondii Mre11 (TgMre11) at the molecular level as a potential therapeutic target. Our results demonstrate that TgMre11 core contains an extended eukaryotic insertion loop that modulates its endonuclease activity, resulting in higher levels compared to its human homologue. This feature likely reflects an adaptation to the parasite´s rapid replication rate during the tachyzoite stage. Additionally, structural and mechanistic similarities with prokaryotic homologues were identified, providing insights into the absence of certain DNA repair partners typically associated with Mre11 in T. gondii. Overall, our findings highlight TgMre11 as a promising candidate for the development of selective inhibitors against pathogenic parasites. (© 2025. The Author(s).) |
| Competing Interests: | Declarations. Competing interests: The authors declare no competing interests. |
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| Grant Information: | PIP-2022-0173 (D.M.R. and V.R.T.) Consejo Nacional de Investigaciones Científicas y Técnicas; R01 AI129807 United States AI NIAID NIH HHS; PICT-2020-SERIEA-00716 (D.M.R.) Agencia Nacional de Promoción Científica y Tecnológica; PICT-2020-SERIEA-01183 (V.R.T.) Agencia Nacional de Promoción Científica y Tecnológica; R01AI129807 (S.O.A. and W.J.S.) National Institutes of Health (NIH-NIAID) |
| Contributed Indexing: | Keywords: TgMre11; Toxoplasma gondii; DNA repair; Insertion loop; Nuclease activity |
| Substance Nomenclature: | 0 (Protozoan Proteins) EC 3.1.- (MRE11 Homologue Protein) 0 (MRE11 protein, human) |
| Entry Date(s): | Date Created: 20251217 Date Completed: 20251218 Latest Revision: 20260612 |
| Update Code: | 20260612 |
| PubMed Central ID: | PMC12712053 |
| DOI: | 10.1038/s41598-025-27759-3 |
| PMID: | 41408384 |
| Βάση Δεδομένων: | MEDLINE |
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