Molecular models of two competitive inhibitors, IL-2δ2 and IL-2δ3, generated by alternative splicing of human interleukin-2

摘要: Molecular models of IL-2delta2 and IL-2delta3, two alternative splice variants human IL-2 without exon 2 3, respectively, are described. These attract particular interest as potential competitive inhibitors the cytokine. Tertiary structure consists four-helix bundle including helices A, B, C D a beta-pleated sheet. Exon encodes A-B loop (Asn30-Lys49 residues) linking A B running in one direction. Rotation helix around putative centre during construction model have not produced any significant changes hydrophobic core molecule. However, large hole was formed on surface molecule instead fold. high affinity receptor is by combination alpha, beta, gamma(c) chains. Comparison bound with has shown that their beta-chain binding sites minimum differences distinct from alpha chain-binding sites. 3 Ala50-Lys97 fragment which forms short connecting loop. Model IL-2delta3 long This composed C-D loops run opposite directions contain beta-strands making Conformation relatively to stabilized creation disulphide bond between cysteines 105 125. In addition, residues beta-sheet interact A-D helical complex close latter contacts solution. absence results insignificant conformational only interacting chain receptor. The beta/gamma(c) heterodimer an intermediate IL-2. Most likely, both naturally occurring antagonists since they keep ability this cytokine fail engage its