SOLUTION STRUCTURE OF AN EXTRACELLULAR DOMAIN-CONTAINING THE WSXWS MOTIF OF THE GRANULOCYTE-COLONY-STIMULATING FACTOR-RECEPTOR AND ITS INTERACTION WITH LIGAND

We have determined the NMR structure of a ligand-binding domain of the granulocyte colony-stimulating factor (G-CSF) receptor, containing th e highly conserved WSxWS motif. The domain consists of seven P-strands with the fibronectin type III-like topology seen in several cytokine receptors. Comparisons between the spectra of the N-15-labelled domain with and without C-CSF indicate that the major ligand-recognition sit e is on the FG loop just upstream of the WSxWS sequence, and not on th e BC loop which is mainly used in the growth hormone system. The WSxWS residues are suggested to contribute to ligand-recognition and to the protein architecture of the G-CSF receptor.