ArticleGenes and immunity2015
A conserved sugar bridge connected to the WSXWS motif has an important role for transport of IL-21R to the plasma membrane.
Article in Genes and immunity, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 25 citations in OpenAlex.
- Untargeted metabolomics reveals immune-metabolic signatures in established cases of rheumatoid arthritis.Frontiers in molecular biosciences · 2026Article
- Differential Binding of ΔFN3 Proteins ofInternational journal of molecular sciences · 2025Article
- The biology of interleukin-6 family cytokines is regulated by glycosylation.The Biochemical journal · 2025Review
- Study of the binding of ΔFN3.1 fragments of theMicrobiome research reports · 2023Article
- ProteinMolecules (Basel, Switzerland) · 2021Review
- The Role of the PFNA Operon of Bifidobacteria in the Recognition of Host's Immune Signals: Prospects for the Use of the FN3 Protein in the Treatment of COVID-19.International journal of molecular sciences · 2021Review
- Genomic Spectrum and Phenotypic Heterogeneity of Human IL-21 Receptor Deficiency.Journal of clinical immunology · 2021Article
- IL-12 and IL-23-Close Relatives with Structural Homologies but Distinct Immunological Functions.Cells · 2020Review
- Article
- ProteinParasitology · 2019Review
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- Protodomains: Symmetry-Related Supersecondary Structures in Proteins and Self-Complementarity.Methods in molecular biology (Clifton, N.J.) · 2019Article
- Apicomplexan C-Mannosyltransferases Modify Thrombospondin Type I-containing Adhesins of the TRAP Family.Glycobiology · 2018Article
- Natural allelic variation of the IL-21 receptor modulates ischemic stroke infarct volume.The Journal of clinical investigation · 2016Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interleukin-21 (IL-21) is a class I cytokine that belongs to the γc-subfamily of cytokines and regulates immune responses. It signals through a heterodimeric receptor complex composed of the IL-21R1 and γc-receptor chains. A characteristic feature of class I cytokine receptors is the presence of a consensus motif WSXWS (WS motif) in the membrane proximal fibronectin type III domain (FNIII) of these receptors. We recently described the structure of the IL-21R:IL-21 complex and showed that the first tryptophan of the WS motif of IL-21R is mannosylated and involved in formation of a sugar bridge that connects the two FNIII domains of the receptor. Furthermore, a mutation within the WS motif of IL-21R was recently shown to cause a novel kind of primary immunodeficiency syndrome (PID). Here, we report the structure of IL-21R alone, which shows that the sugar bridge forms independently of whether IL-21R binds IL-21 or not, and we furthermore investigate the role of this bridge in the export of IL-21R and γC to the plasma membrane. Thus, we provide a molecular explanation for how mutations in the WS motif may cause PIDs.
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