Homology modeling of human leptin/leptin receptor complex.

Leptin receptor mediates the weight regulatory signal carried by the adipocyte-secreted peptide hormone, leptin. It is important to understand the atomic interactions between leptin and the receptor for the therapeutic applications. However, the structure of leptin receptor has not yet been determined. Leptin shows structural similarity to G-CSF, while leptin receptor is similar in amino acid sequence to G-CSF receptor. Because of the similarity between leptin/leptin receptor complex and G-CSF/G-CSF receptor complex, we tried to build a model structure of leptin/leptin receptor complex with the crystal structure of the G-CSF/G-CSF receptor complex as the template. The obtained model for the complex was consistent with the results of the amino acid replacement and deletion experiments. The observation suggests that the model is useful to lead the experimental study on the interaction between leptin and the receptor. Copyright 2000 Academic Press.