Mechanistic and Structural Insights on the IL-15 System through Molecular Dynamics Simulations

Sousa, Rui P.; Laurent, Adèle D.; Quéméner, Agnès; Mortier, Erwan; Le Questel, Jean-Yves

doi:10.3390/molecules24183261

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Mechanistic and Structural Insights on the IL-15 System through Molecular Dynamics Simulations

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Université de Nantes, CEISAM UMR 6230, UFR des Sciences et des Techniques, 2 rue de la Houssinière, BP 92208, F-44000 Nantes, France

CRCINA, CNRS, Inserm, Université d’Angers, Université de Nantes, F-44200 Nantes, France

Immunotherapy, Graft, Oncology (IGO) LabEx, F-44000 Nantes, France

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Nantes Université, CHU Nantes, Inserm, CNRS, SFR Santé, FED 4203, Inserm UMS 016, CNRS UMS 3556, IMPACT Platform, F-44000 Nantes, France

Author to whom correspondence should be addressed.

Academic Editor: Julio Caballero

Molecules 2019, 24(18), 3261; https://doi.org/10.3390/molecules24183261

Received: 19 July 2019 / Revised: 5 September 2019 / Accepted: 6 September 2019 / Published: 6 September 2019

(This article belongs to the Special Issue Computational Methods for Drug Discovery and Design)

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Abstract

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. View Full-Text

Keywords: interleukin 15; IL-15 interfaces; molecular dynamics simulations; protein protein interactions

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MDPI and ACS Style

Sousa, R.P.; Laurent, A.D.; Quéméner, A.; Mortier, E.; Le Questel, J.-Y. Mechanistic and Structural Insights on the IL-15 System through Molecular Dynamics Simulations. Molecules 2019, 24, 3261. https://doi.org/10.3390/molecules24183261

AMA Style

Sousa RP, Laurent AD, Quéméner A, Mortier E, Le Questel J-Y. Mechanistic and Structural Insights on the IL-15 System through Molecular Dynamics Simulations. Molecules. 2019; 24(18):3261. https://doi.org/10.3390/molecules24183261

Chicago/Turabian Style

Sousa, Rui P., Adèle D. Laurent, Agnès Quéméner, Erwan Mortier, and Jean-Yves Le Questel. 2019. "Mechanistic and Structural Insights on the IL-15 System through Molecular Dynamics Simulations" Molecules 24, no. 18: 3261. https://doi.org/10.3390/molecules24183261

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Mechanistic and Structural Insights on the IL-15 System through Molecular Dynamics Simulations

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