3DI2

Crystal structure of the complex of human interleukin-7 with unglycosylated human interleukin-7 receptor alpha ectodomain

Summary for 3DI2

• Entry DOI: 10.2210/pdb3di2/pdb
• Related: 3DI3
• Descriptor: Interleukin-7, Interleukin-7 receptor subunit alpha, PENTAETHYLENE GLYCOL, ... (4 entities in total)
• Functional Keywords: interleukin, cytokine, cytokine receptor, ectodomain, glycoprotein, growth factor, secreted, alternative splicing, disease mutation, membrane, phosphoprotein, polymorphism, receptor, scid, transmembrane, cytokine-cytokine receptor complex, cytokine/cytokine receptor
• Biological source: Homo sapiens (Human); More
• Cellular location: Secreted: P13232; Isoform 1: Cell membrane; Single-pass type I membrane protein. Isoform 3: Cell membrane; Single-pass type I membrane protein. Isoform 4: Secreted: P16871
• Total number of polymer chains: 4
• Total formula weight: 86711.22

Authors

McElroy, C.A.,Dohm, J.A.,Walsh, S.T.R. (deposition date: 2008-06-19, release date: 2009-01-27, Last modification date: 2024-10-30)

Primary citation

McElroy, C.A.,Dohm, J.A.,Walsh, S.T.
Structural and Biophysical Studies of the Human IL-7/IL-7Ralpha Complex.
Structure, 17:54-65, 2009

PubMed 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.

PubMed: 19141282
DOI: 10.1016/j.str.2008.10.019

Experimental method

X-RAY DIFFRACTION (2.7 Å)