Homology modeling study of the human interleukin-7 receptor complex

Following a recent model of human interleukin-7 (IL-7), we presenthere a modeling study of the extracellular part of the humanIL-7 receptor complex, including the IL-7 specific (IL-7R) andthe common gamma (_c) chains. The investigation is based on structuralhomology to the complex of human growth hormone (hGH) boundto its receptor (hGHR). For domain 1 of IL-7R two differentmodels are presented which differ in the alignment to hGHR inthree regions. However, these differences affect binding toIL-7 in only one region, at the interface between loop EF ofdomain 1 of IL-7R and helix C of IL-7. The disulfide patternin domain 1 of IL-7R is predicted to deviate from that observedin hGHR in that the C'–E disulfide (hGHR) is replacedby a C-C' cross-link. The prediction for the _c chain is comparedwith two previous studies. The models of the complex provideinsight into the binding of IL-7 to its receptor and have implicationsfor the suggestion of mutagenesis experiments and the designof (ant)agonists.