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