Nature research paper: Organizing Structural Principles of the Interleukin-17 Ligand-Receptor Axis
The interleukin-17 family of cytokines and receptors play central roles in host defense against infection, and development of inflammatory diseases. The compositions and structures of functional IL-17 family ligand-receptor signaling assemblies remain unclear. Interleukin-17E is a key regulator of Th2 immune responses and driver of inflammatory diseases such as allergic asthma and requires both IL-17 receptor A and IL-17RB to elicit functional responses.
The IL-25–IL-17RB–IL-17RA ternary signaling assembly is a c2-symmetric complex in which the IL-25–IL-17RB homodimer is flanked by two “wing-like” IL-17RA co-receptors through a “tip-to-tip” geometry that is the key receptor-receptor interaction required for initiation of signal transduction. IL-25 interacts solely with IL-17RB to allosterically promote the formation of the IL-17RB–IL-17RA tip-to-tip interface.
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