Title : Structural basis of
receptor sharing by interleukin 17 cytokines
Abstract :
- Interleukin 17 ( IL-17 )-producing helper T cells (T(H)-17 cells), together with their effector cytokines, including members of the IL-17 family, are emerging as key mediators of chronic inflammatory and autoimmune disorders
- Here we present the crystal structure of a complex of IL-17 IL-17 receptor A ( IL-17RA ) bound to IL-17F in a 1:2 stoichiometry
- The mechanism of complex formation was unique for cytokines and involved the engagement of IL-17 by two fibronectin-type domains of IL-17RA in a groove between the IL-17 homodimer interface
- Binding of the first receptor to the IL-17 cytokines modulated the affinity and specificity of the second receptor-binding event, thereby promoting heterodimeric versus homodimeric complex formation
- IL-17RA used a common recognition strategy to bind to several members of the IL-17 family, which allows it to potentially act as a shared receptor in multiple different signaling complexes