The interaction of G-CSF with its receptor.
The function of the G-CSF receptor has been of considerable interest, particularly because of the clinical usefulness of G-CSF. The first step in receptor activation, which is the interaction of G-CSF with its receptor, has been studied by mapping the binding sites of neutralizing antibodies, by studying the complexes formed between G-CSF and various receptor fragments in solution and by mutagenesis of the receptor and ligand. In addition, the structure of G-CSF has been determined. Part of the ligand-binding domain of the receptor in complex with G-CSF has been crystallized and its structure described. Consideration of all these studies has allowed us to make a model of the complete ligand-binding domain in complex with G-CSF that accounts for the published data. The complex has a 2:2 stoichiometry, with two binding sites on both the ligand and receptor that are equivalent to site II and site III of the IL-6 receptor complex. This model was based on the published structure of gp130 in complex with viral IL-6, which we believe to be very similar.
Layton
Judith E
JE
The Ludwig Institute for Cancer Research, Melbourne Tumour Biology Branch, Parkville, Vic., 3050, Australia. jlayton@wehi.edu.au
Hall
Nathan E
NE
D001665:Binding Sites; D003460:Crystallization; D050822:Cytokine Receptor gp130 / Q000737:chemistry; D016179:Granulocyte Colony-Stimulating Factor / Q000737:chemistry / Q000378:metabolism*; D007136:Immunoglobulins; D008024:Ligands; D008956:Models, Chemical; D016297:Mutagenesis, Site-Directed; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000737:chemistry / Q000502:physiology*
D007136:Immunoglobulins; D008024:Ligands; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D050822:Cytokine Receptor gp130; D016179:Granulocyte Colony-Stimulating Factor