The complex of human Gs protein with the beta3 adrenergic receptor: A computer-aided molecular modeling study

Abstract

Three-dimensional (3D) models of the human Gs protein, the human beta3 adrenergic receptor and their complex are constructed using computer-aided molecular modeling techniques. The structures of bacterial EF-tu 200 and bacteriorhodopsin were used as starting points for modeling the Gs protein and beta3 receptor, respectively. Experimental data are used as constraints to guide the modeling. The resulting 3D structures of the Gs protein, the beta3 receptor and their complex are in accord with the experimental data. It is found that the third interacellular loop of the beta3 receptor as well as its C-terminus are involved in the binding. Various residues of N-terminus and C-terminus of the Gs protein also participate in the binding. The model of the complex suggests that the Gs protein binds to the beta3 receptor in such a way that it will be placed in the interface of membrane and intracellular space. This orientation is supported by experimental data. It is concluded that the modeled structure of the complex of the alpha subunit of the human Gs protein and the beta3 adrenergic receptor is in agreement with the experimental data and it can provide a basis for understanding the way these proteins interact.