The crystal structure of human interferon beta at 2.2-angstrom resolution

Type I interferons (IFNs) are helical cytokines that have diverse biological activities despite the fact that they appear to interact with the same receptor system, To achieve a better understanding of the structural basis for the different activities of alpha and beta IFNs, we have determined the crystal structure of glycosylated human IFN-beta at 2.2-Angstrom resolution by molecular replacement, The molecule adopts a fold similar to that of the previously determined structures of murine IFN-beta and human IFN-alpha(2b) but displays several distinct structural features. Like human IFN-alpha(2b), human IFN-beta contains a zinc-binding site at the interface of the two molecules in the asymmetric unit, raising the question of functional relevance for IFN-beta dimers, However, unlike the human IFN-alpha(2b) dimer, in which homologous surfaces form the interface, human IFN-beta dimerizes with contact surfaces from opposite sides of the molecule. The relevance of the structure to the effects of point mutations in IFN-beta at specific exposed residues is discussed, A potential role of ligand-ligand interactions in the conformational assembly of IFN receptor components is discussed.