Three loops of the common γ chain ectodomain required for the binding of interleukin-2 and interleukin-7

Ferenc Olosz, Thomas R. Malek

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

The common γ chain (γc), a subunit of the interleukin (IL)-2, IL-4, IL-7, IL-9, and IL-15 receptors, contributes to both cytokine binding and subsequent signal transduction. Using a model-based site-directed mutagenesis strategy, we have identified residues of the mouse γc extracellular domain that are required for normal γc-dependent enhancement of IL-2 and IL-7 binding. One of these sites, Tyr-103, is homologous to key ligand-interacting residues in the growth hormone and erythropoietin receptors, whereas Cys-161, Cys-210, and Gly-211 may function indirectly by maintaining the functional conformation of γc via formation of an intramolecular disulfide bond. These two cysteines are also required for the integrity of a putative epitope recognized by TUGm2, an antagonistic monoclonal antibody that blocks γc-dependent cytokine binding and bioactivity. These results are consistent with the involvement of three predicted loops in γc that contribute to the binding of both IL-2 and IL-7. Mutations in these loops have also been noted in the γc gene of patients with X-linked severe combined immunodeficiency.

Original languageEnglish (US)
Pages (from-to)30100-30105
Number of pages6
JournalJournal of Biological Chemistry
Volume275
Issue number39
DOIs
StatePublished - Sep 29 2000

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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