3TGX

IL-21:IL21R complex

Summary for 3TGX

• Entry DOI: 10.2210/pdb3tgx/pdb
• Descriptor: Interleukin-21 receptor, Interleukin-21, alpha-D-mannopyranose-(1-6)-alpha-D-mannopyranose-(1-6)-alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[beta-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• Functional Keywords: class i cytokine, class i cytokine receptor, sugarbridge, fibronectin domain, signaling, cytokine-cytokine receptor complex, cytokine/cytokine receptor
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 16
• Total formula weight: 343282.41

Authors

Hamming, O.J.,Kang, L.,Svenson, A.,Karlsen, J.L.,Rahbek-Nielsen, H.,Paludan, S.R.,Hjort, S.A.,Bondensgaard, K.,Hartmann, R. (deposition date: 2011-08-18, release date: 2012-02-15, Last modification date: 2024-11-06)

Primary citation

Hamming, O.J.,Kang, L.,Svensson, A.,Karlsen, J.L.,Rahbek-Nielsen, H.,Paludan, S.R.,Hjorth, S.A.,Bondensgaard, K.,Hartmann, R.
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.
J.Biol.Chem., 2012

PubMed 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.

PubMed: 22235133
DOI: 10.1074/jbc.M111.311084

Experimental method

X-RAY DIFFRACTION (2.8 Å)