The crystal structure of human interferon beta at 2.2-A 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-A resolution by molecular replacement. The molecule adopts a fold similar to that of the previously determined structures of murine IFN-beta and human IFN-alpha2b but displays several distinct structural features. Like human IFN-alpha2b, 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-alpha2b 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.
Karpusas
M
M
Biogen, Inc., 12 Cambridge Center, Cambridge, MA 02142, USA. Michael_Karpusas@biogen.com
Nolte
M
M
Benton
C B
CB
Meier
W
W
Lipscomb
W N
WN
Goelz
S
S
D003198:Computer Simulation; D018360:Crystallography, X-Ray; D004252:DNA Mutational Analysis; D019281:Dimerization; D006023:Glycoproteins / Q000737:chemistry*; D006801:Humans; D016899:Interferon-beta / Q000737:chemistry*; D007372:Interferons / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011487:Protein Conformation
D006023:Glycoproteins; D016899:Interferon-beta; D007372:Interferons