Interleukin-24 is a member of IL-10 family cytokines that is composed of six interleukins and four interferons that share modest homology and similar structures, and interacts with the extracellular Ig domains of heterodimeric type 2 cytokine receptors (CRT2). Cytokines play pivotal roles in communication networks of cells under both normal physiological conditions and various pathological states. Elaboration of the detailed interactions between these cytokines and their corresponding receptors is important for better understanding of immunological processes and for potential use in immunotherapies. Currently, the number of structures of cytokine-receptor complexes is limited and includes only one example of a ternary complex, IL-20/IL-20R1/IL-20R2. Therefore, there is a pressing need for further studies of these systems. Here, we present ongoing efforts towards the production of human IL24 and, prospectively, its complexes with cognate receptors, IL-20/22R1 and IL-20R2 for structural characterization. IL-24 was initially discovered as a tumor suppressor protein and named melanoma differentiation associated gene 7 (MDA-7). Subsequently IL-24 has been found to suppress the proliferation of several cancer cell lines. In addition to other effects, interaction of IL-24 with the heterodimeric receptor, IL-20(22)R1/IL-20R2, initiates a signaling cascade involving the JAK-STAT pathway. A reporter assay employing this pathway is developed to assess the activity of IL-24 upon binding to its receptors presented on the cell membrane. One of the main barriers in structural studies of this system is production of pure, functional, and homogenous IL-24. Our attempts to overcome this problem are presented in this poster.

Production of IL-24 and its receptors for structural studies

253rd National Meeting (2017)

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