The crystal structure of the interleukin 21 receptor bound to interleukin 21 reveals that a sugar chain interacting with the WSXWS motif is an integral part of the interleukin 21 receptor

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  • Ole Jensen Hamming, Danmark
  • Lishan Kang, Novo Nordisk China R&D, Beijing 102206, China, Kina
  • Anders Svensson, Biopharmaceuticals Research Unit, Novo Nordisk A/S, DK-2760 Maaloev, Denmark, Danmark
  • Jesper Lykkegaard Karlsen
  • Henrik Rahbek-Nielsen, Biopharmaceuticals Research Unit, Novo Nordisk A/S, DK-2760 Maaloev, Denmark, Danmark
  • Søren Riis Paludan
  • Siv A Hjorth, Biopharmaceuticals Research Unit, Novo Nordisk A/S, DK-2760 Maaloev, Denmark, Danmark
  • Kent Bondensgaard, Biopharmaceuticals Research Unit, Novo Nordisk A/S, Danmark
  • Rune Hartmann
Interleukin (IL) 21 is a class I cytokine, which 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 gamma chain (gC). 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 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 on the first tryptophan. We furthermore demonstrate that a sugar chain bridge the two fibronectin domains which constitute the extracellular domain of IL-21R and anchors at the WSXWS motif through an extensive hydrogen bonding network, including the mannosylation. The glycan thus transforms the V-shaped receptor into a A-frame. This finding offers a novel structural explanation of the role of the class I cytokine signature motif
OriginalsprogEngelsk
TidsskriftJournal of Biological Chemistry
Vol/bind287
Sider (fra-til)9454-9460
Antal sider7
ISSN0021-9258
DOI
StatusUdgivet - 16 mar. 2012

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