Exploring the NANOG-TET2 interaction interface. Effects of a selected mutation and hypothesis on the clinical correlation with anemias
In this study, we focused on the computational analysis of a selected single-point mutation identified by a NGS screening panel in the TET2 enzyme classified as “variant of uncertain clinical significance.” The mutation, namely Q1084P, occurs at the interface between TET2, an important epigenetic re...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Chemical Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fchbi.2024.1517163/full |
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| author | Claudia Testi Roberta Piacentini Roberta Piacentini Alessandro Perrone Chiara Bartoli Daniele Leso Domitilla Pavia Elisa Pistolesi Flavio Scipione Irene Cotronea Marco Adinolfi Falcone Marco Ierani Alberto Boffi Lorenzo Di Rienzo |
| author_facet | Claudia Testi Roberta Piacentini Roberta Piacentini Alessandro Perrone Chiara Bartoli Daniele Leso Domitilla Pavia Elisa Pistolesi Flavio Scipione Irene Cotronea Marco Adinolfi Falcone Marco Ierani Alberto Boffi Lorenzo Di Rienzo |
| author_sort | Claudia Testi |
| collection | DOAJ |
| description | In this study, we focused on the computational analysis of a selected single-point mutation identified by a NGS screening panel in the TET2 enzyme classified as “variant of uncertain clinical significance.” The mutation, namely Q1084P, occurs at the interface between TET2, an important epigenetic regulator, and NANOG, a transcription factor fundamental for hematopoietic cells differentiation. Notably, the mutation occurs in a protein region distant from the active site; moreover, the experimental structures of the interacting region of both proteins are unknown, making it difficult to validate the impact of TET2 mutation on its binding with NANOG. To address these challenges, we employed an integrated computational approach combining molecular docking, molecular dynamics simulations and protein-protein interaction prediction. Our findings indicate that the single-point mutation might effectively reduce the TET2-NANOG interaction, which would consequently impair cells differentiation and hematopoiesis process, consistent with the clinical presentation of pure red cell aplastic anemia. These results, along with the proposed computational method, provide insights for establishing clinical correlations between variants of uncertain significance and anemias in general, comprising common hematological problems widespread in the world population and for which dedicated NGS panels are still not available. |
| format | Article |
| id | doaj-art-473d7d8baa4046cf8e52b60ffde3717c |
| institution | Kabale University |
| issn | 2813-530X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Chemical Biology |
| spelling | doaj-art-473d7d8baa4046cf8e52b60ffde3717c2025-01-06T06:58:52ZengFrontiers Media S.A.Frontiers in Chemical Biology2813-530X2025-01-01310.3389/fchbi.2024.15171631517163Exploring the NANOG-TET2 interaction interface. Effects of a selected mutation and hypothesis on the clinical correlation with anemiasClaudia Testi0Roberta Piacentini1Roberta Piacentini2Alessandro Perrone3Chiara Bartoli4Daniele Leso5Domitilla Pavia6Elisa Pistolesi7Flavio Scipione8Irene Cotronea9Marco Adinolfi Falcone10Marco Ierani11Alberto Boffi12Lorenzo Di Rienzo13Center for Life Nano and Neuro Science, Istituto Italiano di Tecnologia (IIT), Roma, ItalyDepartment of Biochemical Sciences “Alessandro Rossi Fanelli”, Università “Sapienza”, Roma, ItalyDepartment of Physics, Università “Sapienza”, Roma, ItalyDepartment of Physics, Università “Sapienza”, Roma, ItalyDepartment of Physics, Università “Sapienza”, Roma, ItalyDepartment of Physics, Università “Sapienza”, Roma, ItalyDepartment of Physics, Università “Sapienza”, Roma, ItalyDepartment of Physics, Università “Sapienza”, Roma, ItalyDepartment of Physics, Università “Sapienza”, Roma, ItalyDepartment of Physics, Università “Sapienza”, Roma, ItalyDepartment of Physics, Università “Sapienza”, Roma, ItalyDepartment of Physics, Università “Sapienza”, Roma, ItalyDepartment of Biochemical Sciences “Alessandro Rossi Fanelli”, Università “Sapienza”, Roma, ItalyCenter for Life Nano and Neuro Science, Istituto Italiano di Tecnologia (IIT), Roma, ItalyIn this study, we focused on the computational analysis of a selected single-point mutation identified by a NGS screening panel in the TET2 enzyme classified as “variant of uncertain clinical significance.” The mutation, namely Q1084P, occurs at the interface between TET2, an important epigenetic regulator, and NANOG, a transcription factor fundamental for hematopoietic cells differentiation. Notably, the mutation occurs in a protein region distant from the active site; moreover, the experimental structures of the interacting region of both proteins are unknown, making it difficult to validate the impact of TET2 mutation on its binding with NANOG. To address these challenges, we employed an integrated computational approach combining molecular docking, molecular dynamics simulations and protein-protein interaction prediction. Our findings indicate that the single-point mutation might effectively reduce the TET2-NANOG interaction, which would consequently impair cells differentiation and hematopoiesis process, consistent with the clinical presentation of pure red cell aplastic anemia. These results, along with the proposed computational method, provide insights for establishing clinical correlations between variants of uncertain significance and anemias in general, comprising common hematological problems widespread in the world population and for which dedicated NGS panels are still not available.https://www.frontiersin.org/articles/10.3389/fchbi.2024.1517163/fullanemiaTET2nanogsingle-point mutationsmolecular dynamicsmolecular docking |
| spellingShingle | Claudia Testi Roberta Piacentini Roberta Piacentini Alessandro Perrone Chiara Bartoli Daniele Leso Domitilla Pavia Elisa Pistolesi Flavio Scipione Irene Cotronea Marco Adinolfi Falcone Marco Ierani Alberto Boffi Lorenzo Di Rienzo Exploring the NANOG-TET2 interaction interface. Effects of a selected mutation and hypothesis on the clinical correlation with anemias Frontiers in Chemical Biology anemia TET2 nanog single-point mutations molecular dynamics molecular docking |
| title | Exploring the NANOG-TET2 interaction interface. Effects of a selected mutation and hypothesis on the clinical correlation with anemias |
| title_full | Exploring the NANOG-TET2 interaction interface. Effects of a selected mutation and hypothesis on the clinical correlation with anemias |
| title_fullStr | Exploring the NANOG-TET2 interaction interface. Effects of a selected mutation and hypothesis on the clinical correlation with anemias |
| title_full_unstemmed | Exploring the NANOG-TET2 interaction interface. Effects of a selected mutation and hypothesis on the clinical correlation with anemias |
| title_short | Exploring the NANOG-TET2 interaction interface. Effects of a selected mutation and hypothesis on the clinical correlation with anemias |
| title_sort | exploring the nanog tet2 interaction interface effects of a selected mutation and hypothesis on the clinical correlation with anemias |
| topic | anemia TET2 nanog single-point mutations molecular dynamics molecular docking |
| url | https://www.frontiersin.org/articles/10.3389/fchbi.2024.1517163/full |
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