title: The EM structure of a type I interferon-receptor complex reveals a novel mechanism for cytokine signaling.
abstract: Type I interferons (IFNs) have pleiotropic effects, including antiviral, antiproliferative, and immunomodulatory responses. All type I IFNs 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 IFN alpha2 with the ectodomains of ifnar1 and ifnar2. We present a model of the complex obtained by placing atomic models of subunits into the density map of the complex. The complex of IFN alpha2 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.
authors.affiliation: Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Zongli
authors.initials: Z
authors.lastname: Li
authors.forename: Jennifer Julia
authors.initials: JJ
authors.lastname: Strunk
authors.forename: Peter
authors.initials: P
authors.lastname: Lamken
authors.forename: Jacob
authors.initials: J
authors.lastname: Piehler
authors.forename: Thomas
authors.initials: T
authors.lastname: Walz
mesh_terms: D007370:Interferon Type I / Q000737:chemistry* / Q000235:genetics; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009154:Mutation; D053633:Receptor, Interferon alpha-beta / Q000737:chemistry* / Q000235:genetics; D017471:Receptors, Interferon / Q000737:chemistry* / Q000235:genetics; D015398:Signal Transduction
chemical_list: D007370:Interferon Type I; D017471:Receptors, Interferon; C120411:interferon receptor, type II; D053633:Receptor, Interferon alpha-beta