PMID: 9557946Apr 29, 1998Paper

Molecular models of two competitive inhibitors, IL-2delta2 and IL-2delta3, generated by alternative splicing of human interleukin-2

Immunology Letters
A I DenesyukT Korpela

Abstract

Molecular models of IL-2delta2 and IL-2delta3, two alternative splice variants of human IL-2 without exon 2 and 3, respectively, are described. These alternative splice variants attract particular interest as potential competitive inhibitors of the cytokine. Tertiary structure of IL-2 consists of four-helix bundle including helices A, B, C and D and a beta-pleated sheet. Exon 2 encodes the A-B loop (Asn30-Lys49 residues) linking helices A and B running in one direction. Rotation of the helix A around putative centre during the construction of IL-2delta2 model have not produced any significant changes in the hydrophobic core of IL-2 molecule. However, a large hole was formed on the surface of IL-2delta2 molecule instead of A-B loop in IL-2 fold. A high affinity IL-2 receptor is formed by combination of alpha, beta, and gamma(c) chains. Comparison of the model of the receptor bound IL-2 with the model of IL-2delta2 has shown that their beta-chain binding sites have minimum differences as distinct from alpha and gamma(c) chain-binding sites. Exon 3 encodes Ala50-Lys97 fragment which forms helices B and C with their short connecting loop. Model IL-2delta3 consists of helices A and D and long linking loop. This loop was composed of ...Continue Reading

References

May 25, 1977·Journal of Molecular Biology·F C BernsteinM Tasumi
Oct 30, 1992·Biochemical and Biophysical Research Communications·Y RongS M Liang
Jul 5, 1991·Science·S DavisG D Yancopoulos
Jan 1, 1990·Annual Review of Biochemistry·K I AraiT Yokota
Jul 1, 1990·Trends in Biochemical Sciences·D CosmanC J March
Sep 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·J F Bazan
Oct 1, 1990·Immunology Today·J F Bazan
Jan 1, 1989·Annual Review of Biochemistry·N A Nicola
May 15, 1986·Analytical Biochemistry·J L BrowningJ E Smart
Dec 1, 1983·Proceedings of the National Academy of Sciences of the United States of America·T FujitaT Taniguchi
Mar 15, 1994·Structure·D A RozwarskiP A Karplus
Jan 1, 1993·Annual Review of Immunology·Y MinamiT Taniguchi
Oct 1, 1995·Protein Science : a Publication of the Protein Society·P D LyneW G Richards
Mar 1, 1996·Molecular Immunology·W J AlmsB White
Sep 20, 1996·The Journal of Biological Chemistry·V N TsytsikovB White
Jul 17, 1992·Science·D B McKay

❮ Previous
Next ❯

Citations

Dec 2, 2004·Nature Reviews. Immunology·Kristen W Lynch
Jul 2, 2002·American Journal of Respiratory Cell and Molecular Biology·Michel P BihlMichael Roth
May 12, 2016·Scientific Reports·Lei ZhaoHaiyan Liu
Nov 6, 2007·Proteins·Konstantin A DenessioukMark S Johnson

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alternative splicing

Alternative splicing a regulated gene expression process that allows a single genetic sequence to code for multiple proteins. Here is that latest research.