The interaction of G-CSF with its receptor

Layton, JE; Hall, NE

Author(s): Layton, JE; Hall, NE;
Journal Title: FRONTIERS IN BIOSCIENCE
Publication Type: Journal Article
Abstract: 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.
Publisher: FRONTIERS IN BIOSCIENCE INC
Keywords: COLONY-STIMULATING FACTOR; IMMUNOGLOBULIN-LIKE DOMAIN; SEVERE CONGENITAL NEUTROPENIA; LIGAND-BINDING SITE; CYTOKINE-RECEPTOR; EXTRACELLULAR DOMAIN; EXPRESSION CLONING; DEFICIENT MICE; GCSF-RECEPTOR; 2/2 COMPLEX
Publisher's Version: https://doi.org/10.2741/2041
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2006-09-01 12:00:00