Homology modeling study of the human interleukin-7 receptor complex.
Following a recent model of human interleukin-7 (IL-7), we present here a modeling study of the extracellular part of the human IL-7 receptor complex, including the IL-7 specific (IL-7R) and the common gamma (gamma c) chains. The investigation is based on structural homology to the complex of human growth hormone (hGH) bound to its receptor (hGHR). For domain 1 of IL-7R two different models are presented which differ in the alignment to hGHR in three regions. However, these differences affect binding to IL-7 in only one region, at the interface between loop EF of domain 1 of IL-7R and helix C of IL-7. The disulfide pattern in domain 1 of IL-7R is predicted to deviate from that observed in hGHR in that the C'-E disulfide (hGHR) is replaced by a C-C' cross-link. The prediction for the gamma c chain is compared with two previous studies. The models of the complex provide insight into the binding of IL-7 to its receptor and have implications for the suggestion of mutagenesis experiments and the design of (ant)agonists.
Kroemer
R T
RT
Physical and Theoretical Chemistry Laboratory, University of Oxford, UK.
Richards
W G
WG
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000737:chemistry*; D003198:Computer Simulation; D005069:Evaluation Studies as Topic; D005544:Forecasting; D006801:Humans; D015851:Interleukin-7; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D018123:Receptors, Interleukin / Q000737:chemistry*; D020395:Receptors, Interleukin-7; D015203:Reproducibility of Results; D016415:Sequence Alignment / Q000379:methods; D017386:Sequence Homology, Amino Acid
D015703:Antigens, CD; D015851:Interleukin-7; D018123:Receptors, Interleukin; D020395:Receptors, Interleukin-7