Mechanistic and Structural Insights on the IL-15 System through Molecular Dynamics Simulations
Interleukin 15 (IL-15), a four-helix bundle cytokine, is involved in a plethora of different cellular functions and, particularly, plays a key role in the development and activation of immune responses. IL-15 forms receptor complexes by binding with IL-2Rβ- and common γ (γ...
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MDPI AG
2019-09-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/24/18/3261 |
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| author | Rui P. Sousa Adèle D. Laurent Agnès Quéméner Erwan Mortier Jean-Yves Le Questel |
| author_facet | Rui P. Sousa Adèle D. Laurent Agnès Quéméner Erwan Mortier Jean-Yves Le Questel |
| author_sort | Rui P. Sousa |
| collection | DOAJ |
| description | Interleukin 15 (IL-15), a four-helix bundle cytokine, is involved in a plethora of different cellular functions and, particularly, plays a key role in the development and activation of immune responses. IL-15 forms receptor complexes by binding with IL-2Rβ- and common γ (γc)-signaling subunits, which are shared with other members of the cytokines family (IL-2 for IL-2Rβ- and all other γc- cytokines for γc). The specificity of IL-15 is brought by the non-signaling α-subunit, IL-15Rα. Here we present the results of molecular dynamics simulations carried out on four relevant forms of IL-15: its monomer, IL-15 interacting individually with IL-15Rα (IL-15/IL-15Rα), with IL-2Rβ/γc subunits (IL-15/IL-2Rβ/γc) or with its three receptors simultaneously (IL-15/IL-15Rα/IL-2Rβ/γc). Through the analyses of the various trajectories, new insights on the structural features of the interfaces are highlighted, according to the considered form. The comparison of the results with the experimental data, available from X-ray crystallography, allows, in particular, the rationalization of the importance of IL-15 key residues (e.g., Asp8, Lys10, Glu64). Furthermore, the pivotal role of water molecules in the stabilization of the various protein-protein interfaces and their H-bonds networks are underlined for each of the considered complexes. |
| first_indexed | 2024-04-14T00:10:18Z |
| format | Article |
| id | doaj.art-24cbb43a400647d58ca6a53cab8a4962 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-14T00:10:18Z |
| publishDate | 2019-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-24cbb43a400647d58ca6a53cab8a49622022-12-22T02:23:21ZengMDPI AGMolecules1420-30492019-09-012418326110.3390/molecules24183261molecules24183261Mechanistic and Structural Insights on the IL-15 System through Molecular Dynamics SimulationsRui P. Sousa0Adèle D. Laurent1Agnès Quéméner2Erwan Mortier3Jean-Yves Le Questel4Université de Nantes, CEISAM UMR 6230, UFR des Sciences et des Techniques, 2 rue de la Houssinière, BP 92208, F-44000 Nantes, FranceUniversité de Nantes, CEISAM UMR 6230, UFR des Sciences et des Techniques, 2 rue de la Houssinière, BP 92208, F-44000 Nantes, FranceCRCINA, CNRS, Inserm, Université d’Angers, Université de Nantes, F-44200 Nantes, FranceCRCINA, CNRS, Inserm, Université d’Angers, Université de Nantes, F-44200 Nantes, FranceUniversité de Nantes, CEISAM UMR 6230, UFR des Sciences et des Techniques, 2 rue de la Houssinière, BP 92208, F-44000 Nantes, FranceInterleukin 15 (IL-15), a four-helix bundle cytokine, is involved in a plethora of different cellular functions and, particularly, plays a key role in the development and activation of immune responses. IL-15 forms receptor complexes by binding with IL-2Rβ- and common γ (γc)-signaling subunits, which are shared with other members of the cytokines family (IL-2 for IL-2Rβ- and all other γc- cytokines for γc). The specificity of IL-15 is brought by the non-signaling α-subunit, IL-15Rα. Here we present the results of molecular dynamics simulations carried out on four relevant forms of IL-15: its monomer, IL-15 interacting individually with IL-15Rα (IL-15/IL-15Rα), with IL-2Rβ/γc subunits (IL-15/IL-2Rβ/γc) or with its three receptors simultaneously (IL-15/IL-15Rα/IL-2Rβ/γc). Through the analyses of the various trajectories, new insights on the structural features of the interfaces are highlighted, according to the considered form. The comparison of the results with the experimental data, available from X-ray crystallography, allows, in particular, the rationalization of the importance of IL-15 key residues (e.g., Asp8, Lys10, Glu64). Furthermore, the pivotal role of water molecules in the stabilization of the various protein-protein interfaces and their H-bonds networks are underlined for each of the considered complexes.https://www.mdpi.com/1420-3049/24/18/3261interleukin 15IL-15 interfacesmolecular dynamics simulationsprotein protein interactions |
| spellingShingle | Rui P. Sousa Adèle D. Laurent Agnès Quéméner Erwan Mortier Jean-Yves Le Questel Mechanistic and Structural Insights on the IL-15 System through Molecular Dynamics Simulations Molecules interleukin 15 IL-15 interfaces molecular dynamics simulations protein protein interactions |
| title | Mechanistic and Structural Insights on the IL-15 System through Molecular Dynamics Simulations |
| title_full | Mechanistic and Structural Insights on the IL-15 System through Molecular Dynamics Simulations |
| title_fullStr | Mechanistic and Structural Insights on the IL-15 System through Molecular Dynamics Simulations |
| title_full_unstemmed | Mechanistic and Structural Insights on the IL-15 System through Molecular Dynamics Simulations |
| title_short | Mechanistic and Structural Insights on the IL-15 System through Molecular Dynamics Simulations |
| title_sort | mechanistic and structural insights on the il 15 system through molecular dynamics simulations |
| topic | interleukin 15 IL-15 interfaces molecular dynamics simulations protein protein interactions |
| url | https://www.mdpi.com/1420-3049/24/18/3261 |
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