Structural and Biophysical Studies of the Human IL-7/IL-7Rα Complex

By C. McElroy, J. A. Dohm, Scott T R Walsh. 2009

96 citations recorded by the source corpus.

Summary IL-7 and IL-7Rα bind the γc receptor forming a complex crucial to several signaling cascades leading to the development and homeostasis of T and B cells. We report the IL-7Rα ectodomain uses glycosylation to modulate its binding constants to IL-7, unlike the other receptors in the γc family. IL-7 binds glycosylated IL-7Rα 300-fold more tightly than unglycosylated IL-7Rα, and the enhanced affinity is attributed primarily to an accelerated on-rate. Structural comparison of IL-7 in complex to both forms of the IL-7Rα reveals that glycosylation does not participate directly in the binding interface. The SCID mutations of the IL-7Rα locate outside the binding interface with IL-7 suggesting that the expressed mutations cause protein folding defects in IL-7Rα. The IL-7/IL-7Rα structures provide the first view 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.

Subfields: Immunology, Radiology, Nuclear Medicine and Imaging

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I. Marković

Citations in the corpus

Modulation of Signaling Mediated by TSLP and IL-7 in Inflammation, Autoimmune Diseases, and Cancer (2020, background): “Structural data shows burial of the only tryptophan residue of IL-7 in the hydrophobic core of the helix bundle, consistent with mutagenesis studies that linked this position to the proper folding of IL-7 (99, 113, 114).”