Structure function analysis of interleukin 7: Requirement for an aromatic ring at position 143 of helix D

Johanna C. VanderSpek, John A. Sutherland, Brian M. Gill, Gullu Gorgun, Francine M. Foss, John R. Murphy

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

The residues located at the carboxyl terminus of helix D in interleukin-7 (IL-7) have previously been targeted as important for recruitment and binding to the γ chain component of the IL-7 receptor (IL-7R). In this study, Trp 143 of helix D was mutated to His, Phe, Tyr and Pro and these mutants, along with a W143A mutant previously described, were studied to determine the effects on activation of DNA synthesis and binding affinity to IL-7R positive 2E8 cells. The W143F and W143Y mutants were similar to wild type IL-7 in their binding properties and retained 85% and 74% of their activating properties, respectively. In contrast, the W143H mutant possessed a lower binding affinity and a corresponding decrease in activation, the W143A mutant possessed an over 100-fold decreased binding affinity and some residual activation activity and the W143P mutant possessed a greatly decreased binding affinity and did not activate. These results strongly suggest an aromatic residue is required at position 143 for IL-7R binding and subsequent signal transduction.

Original languageEnglish (US)
Pages (from-to)227-233
Number of pages7
JournalCytokine
Volume17
Issue number5
DOIs
StatePublished - Jan 1 2002

Keywords

  • IL-7
  • Mutational analysis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Hematology
  • Molecular Biology

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    VanderSpek, J. C., Sutherland, J. A., Gill, B. M., Gorgun, G., Foss, F. M., & Murphy, J. R. (2002). Structure function analysis of interleukin 7: Requirement for an aromatic ring at position 143 of helix D. Cytokine, 17(5), 227-233. https://doi.org/10.1006/cyto.2002.1004