The EM structure of a type I interferon – receptor complex reveals a novel mechanism for cytokine signaling

摘要

Type I interferons have pleiotropic effects, including antiviral, antiproliferative and immunomodulatory responses. All type I interferons bind to a shared receptor consisting of the two transmembrane proteins ifnar1 and ifnar2. We used negative stain electron microscopy to calculate a three-dimensional reconstruction of the ternary complex formed by a triple mutant interferon-α2 with the ectodomains of ifnar1 and ifnar2. We present a model of the complex obtained by placing atomic models of the subunits into the density map of the complex. The complex of interferon-α2 with its receptor, a class II cytokine receptor, shows structural similarities to the complexes formed by growth hormone and erythropoietin with their receptors, members of the class I cytokine receptor family. Despite different assembly mechanisms, class I and class II cytokine receptors thus appear to initiate signaling through similar arrangements of the receptors induced by the binding of their respective ligands.