Type I interferon structures: Possible scaffolds for the interferon-alpha receptor complex

The structures of several type I interferons (IFNs) are known. We review the structural information known for IFN alphas and compare them to other interferons and cytokines. We also review the structural information known or proposed for IFN-cell receptor complexes. However, the structure of the IFN - cell receptor - IFN receptor2 (IFNAR2) and IFN receptor1 (IFNAR1) complex has not yet been determined. This paper describes a structural model of human IFN-IFNAR2/IFNAR1 complex using human IFN-alpha(2b) dimer as the ligand. Both the structures of recombinant human IFN-alpha(2b) and IFN-beta were determined by X-ray crystallography as zinc-mediated dimers. Our proposed model was generated using human IFN-alpha(2b) dimer docked with IFNAR2/IFNAR1. We compare our model with the receptor complex models proposed for IFN-beta and IFN-gamma to contrast similarities and differences. The mutual binding sites of human IFN-alpha(2b) and IFNAR2/IFNAR1 complex are consistent with available mutagenesis studies.