The IL-10R2 binding hot spot on IL-22 is located on the N-terminal helix and is dependent on N-linked glycosylation

Academic Article

Abstract

  • IL-22 is a class 2 α-helical cytokine involved in the generation of inflammatory responses. These activities require IL-22 to engage the cell surface receptors IL-22R1 and the low-affinity signaling molecule IL-10R2. IL-10R2 also interacts with five other class 2 cytokines: IL-10, IL-26, and the interferon-like cytokines IL-28A, IL-28B, and IL-29. Here, we define the IL-10R2 binding site on IL-22 using surface plasmon resonance (SPR) and site-directed mutagenesis. Surprisingly, the binding hot spot on IL-22 includes asparagine 54 (N54), which is post-translationally modified by N-linked glycosylation. Further characterization of the glycosylation reveals that only a single fucosylated N-acetyl glucosamine on N54 is required for maximal IL-10R2 binding. Biological responses of IL-22 mutants measured in cell-based luciferase assays correlate with the in vitro SPR studies. Together, these data suggest that IL-22 activity may be modulated via changes in the glycosylation state of the ligand during inflammation. © 2004 Elsevier Ltd. All rights reserved.
  • Published In

    Digital Object Identifier (doi)

    Author List

  • Logsdon NJ; Jones BC; Allman JC; Izotova L; Schwartz B; Pestka S; Walter MR
  • Start Page

  • 503
  • End Page

  • 514
  • Volume

  • 342
  • Issue

  • 2