Steve Ealick's Research Group
Interferon-γ/Interferon-γ Receptor Complex
PDB file: 1FG9
Molecular interactions among cytokines and cytokine receptors form the basis of many cell-signaling pathways relevant to immune function. Interferon-γ (IFN-γ) signals through a multimeric receptor-complex consisting of two different but structurally related transmembrane chains: the high-affinity receptor-binding subunit (IFN-γRα) and a species-specific accessory factor (AF-1 or IFNγRβ>). The crystal structure of the complex of human IFN-γ with the soluble, glycosylated extracellular part of IFN-γRα (sIFN-γR has been determined at 2.9 Å resolution using multiwavelength anomalous diffraction methods. In addition to the expected 2:1 complex, the crystal structure reveals the presence of a third receptor molecule not directly associated with the IFN-γ dimer. Two distinct intermolecular contacts, involving the edge strands of the C-terminal domains, are observed between this extra receptor and the 2:1 receptor-ligand complex thereby forming a 3:1 complex.
This diagram is of the 3:1 sIFN-γRαIFN-γ complex. The complex is formed by combining the 2:1 complex with receptor R3.
The IFN-γ dimer is composed of two nearly identical monomers, which are similar to that previously reported for the free and bound forms.
Thiel DJ, le Du M-H, Walter RL, D'Arcy A, Chène C, Fountoulakis M, Garotta G, Winkler FK, Ealick SE. Observation of an Unexpected Third Receptor Molecule in the Crystal Structure of Human Interferon-g Receptor Complex. Structure 8:927-936 (2000).