Structural and biophysical studies of the human IL-7/IL-7Ralpha complex

Structure. 2009 Jan 14;17(1):54-65. doi: 10.1016/j.str.2008.10.019.


IL-7 and IL-7Ralpha bind the gamma(c) receptor, forming a complex crucial to several signaling cascades leading to the development and homeostasis of T and B cells. We report that the IL-7Ralpha ectodomain uses glycosylation to modulate its binding constants to IL-7, unlike the other receptors in the gamma(c) family. IL-7 binds glycosylated IL-7Ralpha 300-fold more tightly than unglycosylated IL-7Ralpha, and the enhanced affinity is attributed primarily to an accelerated on rate. Structural comparison of IL-7 in complex to both forms of IL-7Ralpha reveals that glycosylation does not participate directly in the binding interface. The SCID mutations of IL-7Ralpha locate outside the binding interface with IL-7, suggesting that the expressed mutations cause protein folding defects in IL-7Ralpha. The IL-7/IL-7Ralpha structures provide a window into the molecular recognition events of the IL-7 signaling cascade and provide sites to target for designing new therapeutics to treat IL-7-related diseases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biophysics
  • Biosensing Techniques
  • Enzyme-Linked Immunosorbent Assay
  • Glycosylation
  • Humans
  • Interleukin-7 / chemistry*
  • Interleukin-7 Receptor alpha Subunit / chemistry*
  • Protein Conformation


  • Interleukin-7
  • Interleukin-7 Receptor alpha Subunit

Associated data

  • PDB/3DI2
  • PDB/3DI3