title: Comparison of the 3D models of four different human IL-7 isoforms with human and murine IL-7.
abstract: The three-dimensional (3D) models of several alternatively spliced isoforms (ISO1 through ISO4) of human interleukin-7 (hIL-7) are presented. They are based on sequences of mRNA recently discovered in follicular dendritic cells (FDC) and primary cultures of endothelial cells or smooth muscle cells. The structures were docked to a previous model of the human IL-7 receptor, containing the IL-7 specific (IL-7R) and common gamma (gamma(c)) chain. Two different models of murine IL-7 (mIL-7) were generated as well and docked to this receptor. For an evaluation of the structures and the possible biological role of the isoforms, the models were analysed in detail and a series of enthalpy calculations was carried out. Compared with hIL-7, ISO1 appears to bind equally well to hIL-7R, but even better to the gamma(c) chain. This suggests an agonist role of ISO1, which has already been shown experimentally. The prediction that ISO2 exhibits reduced affinity to hIL-7R is supported by experiments where it had been shown to be inactive in a human test system. However, ISO2 as well as ISO3 could represent antagonists for hIL-7. Remarkably, mIL-7 appears to bind significantly less well to hIL-7R, which is in line with experimental observations that it is not active in the human system. The sequences of the isoforms support the helix assignment made for the previous hIL-7 model.
authors.affiliation: Physical and Theoretical Chemistry Laboratory, University of Oxford, UK.
authors.forename: R T
authors.initials: RT
authors.lastname: Kroemer
authors.forename: R
authors.initials: R
authors.lastname: Kröncke
authors.forename: J
authors.initials: J
authors.lastname: Gerdes
authors.forename: W G
authors.initials: WG
authors.lastname: Richards
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D015851:Interleukin-7 / Q000737:chemistry*; D007536:Isomerism; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid
chemical_list: D015851:Interleukin-7