ArticleThe Journal of biological chemistry2012
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.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 88 citations in OpenAlex.
- Article
- From a single C-mannose to multiple C-mannosyltransferases.The Journal of biological chemistry · 2026Review
- An engineered IL-21 variant is a potent antitumor candidate for antitumor immunotherapy.Acta pharmacologica Sinica · 2026Article
- Design of a potent interleukin-21 mimic for cancer immunotherapy.Science immunology · 2025Article
- Methods for detecting, building, and improving tryptophan mannosylation in glycoprotein structures.Protein science : a publication of the Protein Society · 2025Article
- Review
- Structure, sequon recognition and mechanism of tryptophan C-mannosyltransferase.Nature chemical biology · 2023Article
- Article
- Interleukin 21 Receptor Affects Adipogenesis of Human Adipose-Derived Stem/Stromal Cells.Stem cells international · 2022Article
- ProteinMolecules (Basel, Switzerland) · 2021Review
- Genomic Spectrum and Phenotypic Heterogeneity of Human IL-21 Receptor Deficiency.Journal of clinical immunology · 2021Article
- Implications of a 'Third Signal' in NK Cells.Cells · 2021Review
- Yeast- and antibody-based tools for studying tryptophan C-mannosylation.Nature chemical biology · 2021Article
- A method for making alignments of related protein sequences that share very little similarity; shark interleukin 2 as an example.Immunogenetics · 2021Review
- The role of Th17 cells in psoriasis.Immunologic research · 2020Review
- Article
- Structural Understanding of Interleukin 6 Family Cytokine Signaling and Targeted Therapies: Focus on Interleukin 11.Frontiers in immunology · 2020Review
- Engineered IL-21 Cytokine Muteins Fused to Anti-PD-1 Antibodies Can Improve CD8+ T Cell Function and Anti-tumor Immunity.Frontiers in immunology · 2020Article
- Article
- Metabolomics reveals elevated urinary excretion of collagen degradation and epithelial cell turnover products in irritable bowel syndrome patients.Metabolomics : Official journal of the Metabolomic Society · 2019Article
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Authors and funding
9 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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