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 the highly conserved WSxWS motif. The domain consists of seven beta-strands with the fibronectin type III-like topology seen in several cytokine receptors. Comparisons between the spectra of the 15N-labelled domain with and without G-CSF indicate that the major ligand-recognition site is on the FG loop just upstream of the WSxWS sequence, and not on the 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.
Yamasaki
K
K
Protein Engineering Research Institute, Osaka, Japan. kyamasak@nibh.go.jp
Naito
S
S
Anaguchi
H
H
Ohkubo
T
T
Ota
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D017124:Conserved Sequence; D019143:Evolution, Molecular; D016179:Granulocyte Colony-Stimulating Factor / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D018121:Receptors, Cytokine / Q000737:chemistry / Q000378:metabolism; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000737:chemistry* / Q000378:metabolism*; D011986:Receptors, Somatotropin / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012996:Solutions
D008024:Ligands; D018121:Receptors, Cytokine; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D011986:Receptors, Somatotropin; D012996:Solutions; D016179:Granulocyte Colony-Stimulating Factor