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 :
- IL-21 is a class I cytokine that exerts pleiotropic effects on both innate and adaptive immune responses
- It signals through a heterodimeric receptor complex consisting of the IL-21 receptor ( IL-21R ) and the common γ-chain
- A hallmark of the class I cytokine receptors is the class I cytokine receptor signature motif (WSXWS)
- 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
- Furthermore, the WXXW motif is known to be a consensus sequence for C-mannosylation
- 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
- 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
- The glycan thus transforms the V-shaped receptor into an A-frame
- This finding offers a novel structural explanation of the role of the class I cytokine signature motif
Output (sent_index, trigger,
protein,
sugar,
site):
- 6. C-mannosylated, , -, -, motif
- 6. C-mannosylated, , -, -, tryptophan
Output(Part-Of) (sent_index,
protein,
site):
- 3. receptor, motif
- 3. receptors, motif
- 6. IL-21R, motif
- 7. IL-21R, domain
- 7. fibronectin, domains
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):