PMID: 19838198

 

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Title : Structural basis of receptor sharing by interleukin 17 cytokines

Abstract :
  1. 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
  2. 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
  3. 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
  4. 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
  5. 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