Docking of Human Interleukin-15 to its Specific Receptor α Chain: Correlation Between Molecular Modeling and Mutagenesis Experimental Data - Inserm - Institut national de la santé et de la recherche médicale Access content directly
Journal Articles Proteins - Structure, Function and Bioinformatics Year : 2006

Docking of Human Interleukin-15 to its Specific Receptor α Chain: Correlation Between Molecular Modeling and Mutagenesis Experimental Data

Abstract

A structural model of the sushi domain of IL-15Rα was first obtained by homology modeling to study its interactions with IL-15 by means of molecular modeling, peptide scanning, and site-directed mutagenesis. From these experimental data, a putative interacting surface of IL-15Rα with a previously published IL-15 model was inferred: Leu25, Leu44, and Glu46 of IL-15 and Arg35 of IL-15Rα were found to be key interfacial residues and were subsequently used as filters for the construction of docking solutions. Human IL-15/IL-15Rα complexes were constructed in two stages, with a preliminary docking procedure, treating the two partners as rigid bodies and using these filters. In this first stage, two classes of docking solutions were characterized. From a topological point of view, each solution could be derived from the other by reverse orientation of one partner in relation to the other. In a second stage, several further energy refinements clearly favored one solution. Moreover, this unique docking solution was confirmed by molecular modeling of IL-15 mutants previously built and tested in our laboratory. Finally, this complex model, which is a useful tool to study the IL-15/IL-15Rα interface, was topologically compared to IL-2/IL-2Rα complexes (previous model in the literature and recent crystal structure).
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Dates and versions

inserm-02442432 , version 1 (16-01-2020)

Identifiers

  • HAL Id : inserm-02442432 , version 1

Cite

Agnès Quéméner, Jérôme Bernard, Erwan Mortier, Ariane Plet, Yannick Jacques, et al.. Docking of Human Interleukin-15 to its Specific Receptor α Chain: Correlation Between Molecular Modeling and Mutagenesis Experimental Data. Proteins - Structure, Function and Bioinformatics, 2006, 65 (3), pp.623. ⟨inserm-02442432⟩
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