PMID: 22235133

 

    Legend: Sugar

Title : Crystal structure of interleukin-21 receptor ( IL-21R ) bound to IL-21 reveals that sugar chain interacting with WSXWS motif is integral part of IL-21R

Abstract :
  1. IL-21 is a class I cytokine that exerts pleiotropic effects on both innate and adaptive immune responses
  2. It signals through a heterodimeric receptor complex consisting of the IL-21 receptor ( IL-21R ) and the common γ-chain
  3. A hallmark of the class I cytokine receptors is the class I cytokine receptor signature motif (WSXWS)
  4. The exact role of this motif has not been determined yet; however, it has been implicated in diverse functions, including ligand binding, receptor internalization, proper folding, and export, as well as signal transduction
  5. Furthermore, the WXXW motif is known to be a consensus sequence for C-mannosylation
  6. Here, we present the crystal structure of IL-21 bound to IL-21R and reveal that the WSXWS motif of IL-21R is C-mannosylated at the first tryptophan
  7. We furthermore demonstrate that a sugar chain bridges the two fibronectin domains that constitute the extracellular domain of IL-21R and anchors at the WSXWS motif through an extensive hydrogen bonding network, including mannosylation
  8. The glycan thus transforms the V-shaped receptor into an A-frame
  9. This finding offers a novel structural explanation of the role of the class I cytokine signature motif