The interferon-gamma receptor extracellular domain. Non-identical requirements for ligand binding and signaling.
The human interferon-gamma receptor (hIFN-gamma R) extracellular domain interacts in a species-specific manner with both its ligand and an accessory factor encoded on human chromosome 21. Mutant interferon-gamma receptors were constructed by homolog-scanning mutagenesis, replacing segments of the human extracellular domain with the corresponding murine sequence. Replacement of hIFN-gamma R amino acids 1-100, 100-132, 134-183, or 183-245 abolished binding to human interferon-gamma (hIFN-gamma). However, replacement of hIFN-gamma R amino acids 134-209, 183-209, 134-153, 153-167, or 167-183 or deletion of residues 156-165 affected hIFN-gamma binding only partially or not at all. Receptors that bound hIFN-gamma were tested for their ability to signal a functional response, induction of major histocompatibility complex class I antigen expression. Replacement of residues 134-209 greatly reduced the ability of the receptor to signal. This signaling defect could not be attributed solely to a reduction in affinity for ligand and could not be localized to any subregion.
Axelrod
A
A
Department of Molecular Biology, Genentech, Inc., South San Francisco, California 94080.
Gibbs
V C
VC
Goeddel
D V
DV
D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002460:Cell Line; D002891:Chromosomes, Human, Pair 21; D015870:Gene Expression; D006801:Humans; D006822:Hybrid Cells; D007371:Interferon-gamma / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D008024:Ligands; D051379:Mice; D008961:Models, Structural; D010957:Plasmids; D017433:Protein Structure, Secondary; D011869:Radioligand Assay; D017471:Receptors, Interferon / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins; D013045:Species Specificity; D014162:Transfection; D000096743:Interferon gamma Receptor
D007371:Interferon-gamma; D008024:Ligands; D017471:Receptors, Interferon; D011994:Recombinant Proteins; D000096743:Interferon gamma Receptor