REFINED CRYSTAL-STRUCTURE OF RECOMBINANT MURINE INTERFERON-BETA AT 2.15 ANGSTROM RESOLUTION

The crystal structure of recombinant murine interferon-beta (reMuIFN-b eta) has been refined at 2.15 Angstrom resolution using newly collecte d synchrotron data. Based on 11,228 reflections (8.0 to 2.15 Angstrom) , a final R-factor of 19.1% (with a free R-factor of 25.8%) was obtain ed with a model obeying standard geometry within 0.013 Angstrom in bon d lengths and 1.4 degrees in bond angles. Compared with the previously reported model, several amino acid residues in helix A are frame-shif ted, the conformations are changed for parts of loops AB and BC, helix C is extended and a new short helix exists in loop CD. Evolutionary c onsiderations taken together, the type I interferons appear to share c ommon structural features with respect to the chain-folding topology a nd the hydrogen-bond networks between various polypeptide segments. Sp ecifically, the disposition of the C-terminal segment of loop AB (afte r Arg33), known to be an important receptor-binding site, seems to be strictly maintained among the type I interferons. The exposed amino ac id residues on helices A and C, which have recently been implicated as the binding site for another receptor molecule, are less well conserv ed. This may be responsible for varied cellular effects among the subt ypes of type I interferons. (C) 1995 Academic Press Limited