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
References
Nov 1, 1992·The Journal of Clinical Investigation·K KaushanskyM K Pearce
Dec 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·A F LopezM A Vadas
Jan 17, 1992·Science·A M de VosA A Kossiakoff
Dec 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·K HayashidaA Miyajima
Feb 1, 1992·The Journal of Experimental Medicine·C ClaybergerA M Krensky
Mar 1, 1991·Journal of Molecular Recognition : JMR·D A ParryS J Leach
Sep 20, 1991·Cell·T KitamuraA Miyajima
Sep 20, 1991·Cell·J TavernierG Plaetinck
Dec 20, 1991·Science·K DiederichsP A Karplus
Dec 14, 1989·Gene·J A PhillipsM F Shannon
Aug 1, 1989·Journal of Cellular Physiology·T KitamuraF Takaku
Jul 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·I LamontJ B Egan
Sep 1, 1988·Journal of Cellular Physiology·T G GesnerS C Clark
Nov 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·I Clark-LewisS B Kent
Jun 5, 1987·Science·S C Clark, R Kamen
Dec 1, 1983·Biopolymers·W Kabsch, C Sander
Dec 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·E I KorpelainenA F Lopez
Oct 6, 1995·The Journal of Biological Chemistry·P O OlinsJ A Klover
May 16, 1995·Biochemistry·Y FengC A McWherter
Jul 1, 1994·Molecular and Cellular Biology·F W QuelleJ N Ihle
Jun 21, 1994·Proceedings of the National Academy of Sciences of the United States of America·T R HercusA F Lopez
Sep 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·O SilvennoinenJ N Ihle
Jan 1, 1993·Growth Factors·G J GoodallA F Lopez
Jun 1, 1996·Molecular and Cellular Biology·F C StomskiA F Lopez
Nov 1, 1994·Acta Crystallographica. Section D, Biological Crystallography·E A Merritt, M E Murphy
Citations
Dec 3, 1999·The International Journal of Biochemistry & Cell Biology·J M WoodcockA F Lopez
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
Apr 9, 2009·PloS One·Raja DeyLin Chen