Contributions of cloned type I interferon receptor subunits to differential ligand binding.
The human type I interferons, including at least 12 IFN-alphas, IFN-beta and IFN-omega, bind to a receptor (IFNAR) composed of at least two transmembrane subunits, IFNAR-1 and IFNAR-2. The contributions of the receptor subunits to ligand binding were investigated by measuring the binding properties of IFNAR-1 or IFNAR-2 alone, or when co-expressed. The affinity of IFNAR-2 for IFN-alpha2 was increased by the co-expression of IFNAR-1, which itself binds ligand very weakly. Most type I IFNs inhibited the binding of IFN-alpha2 to IFNAR-2 alone with IC50 values of 2-20 nM. For cells co-expressing IFNAR-1 and IFNAR-2, the IC50 values decreased 3-20-fold for various ligands, relative to their values on IFNAR-2 alone. Thus, while IFNAR-2 plays the major role in affinity determination and differential recognition of type I IFNs, IFNAR-1 modulates both the ligand affinity and selectivity of the IFNAR-1/IFNAR-2 receptor complex.
Cutrone
E C
EC
Department of Molecular Genetics and Microbiology, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
Langer
J A
JA
D000818:Animals; D001667:Binding, Competitive; D019556:COS Cells; D003001:Cloning, Molecular; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism*; D016898:Interferon-alpha / Q000378:metabolism*; D016899:Interferon-beta / Q000378:metabolism*; D007700:Kinetics; D046911:Macromolecular Substances; D008565:Membrane Proteins; D011869:Radioligand Assay; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D014162:Transfection
C507964:IFNAR1 protein, human; D007370:Interferon Type I; D016898:Interferon-alpha; D046911:Macromolecular Substances; D008565:Membrane Proteins; D017471:Receptors, Interferon; D011994:Recombinant Proteins; C063743:interferon omega 1; D053633:Receptor, Interferon alpha-beta; D016899:Interferon-beta