A discontinuous eight-amino acid epitope in human interleukin-3 binds the alpha-chain of its receptor.

The Journal of Biological Chemistry
C J BagleyA F Lopez

Abstract

We have previously reported that, within the first helix of human interleukin (IL)-3, residues Asp21 and Glu22 are important for interaction with the alpha- and beta-chains of the IL-3 receptor, respectively. In order to define more precisely the sites of interaction with the receptor, we have performed molecular modeling of the helical core of IL-3 and single amino acid substitution mutagenesis of residues predicted to lie on the surfaces of the A, C, and D helices. The resulting analogues were characterized for their abilities to stimulate proliferation of TF-l cells and for binding to the high affinity (alpha- and beta-chain; IL-3Ralpha/Rbeta) or low affinity (alpha-chain alone; IL-3Ralpha) IL-3 receptor. We found that in addition to Asp21, residues Ser17, Asn18, and Thr25 within the A helix and Arg108, Phe113, Lys116, and Glu119 within the D helix of IL-3 were important for biological activity. Analysis of their binding characteristics revealed that these analogues were deficient in binding to both the IL-3Ralpha/Rbeta and the IL-3Ralpha forms of the receptor, consistent with a selective impairment of interaction with IL-3Ralpha. Molecular modeling suggests that these eight amino acid residues are adjacent in the tertiary s...Continue Reading

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Citations

Jul 16, 2008·Immunology and Cell Biology·Deirdre R Coombe
May 18, 2010·The Journal of Biological Chemistry·Shamaruh MirzaIan G Young
Nov 9, 2001·Biochemical and Biophysical Research Communications·B K KleinJ P McKearn
Oct 11, 2012·Immunological Reviews·Sophie E BroughtonMichael W Parker
Sep 5, 1997·The Journal of Biological Chemistry·B K KleinJ P McKearn
Jul 3, 2002·The Journal of Biological Chemistry·Jean-Pierre ZanettaGérard Vergoten

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