Crystal structure of ovine interferon-tau at 2.1 angstrom resolution

Ovine interferon-tau (ovIFN-tau) is a pregnancy recognition hormone require d for normal embryonic development in sheep. In addition to its novel role in reproductive physiology, ovIFN-tau displays antiviral and antiproliferat ive activities similar to the IFN-alpha, subtypes. To probe the structural basis for its unique activity profile, the crystal structure of ovIFN-tau h as been determined at 2.1 A resolution. The fold of ovIFN-tau is similar to the previously determined crystal structures of human IFN-alpha(2b) and hu man and murine IFN-beta, which each contain five alpha-helices. Comparison of ovIFN-tau with huIFN-alpha(2b), huIFN-beta, and muIFN-beta reveals unexp ected structural differences that occur in regions of considerable sequence identity. Specifically, main-chain differences up to 11 Angstrom occur for residues in helix A, the AB loop, helix B, and the BC loop. Furthermore, t hese regions are known to be important for receptor binding and biological activity. Of particular interest, a buried ion pair is observed in ovIFN-ta u between Glu71 and Arg145 which displaces a conserved tryptophan residue ( Trp77) from the helical bundle core. This ion pair represents a major chang e in the core of ovIFN-tau compared to huIFN-alpha(2b). Based on amino acid sequence comparisons, these ovIFN-tau structural features may be conserved in several human IFN-alpha subtypes and IFN-omega. The structure identifie s potential problems in interpreting site-directed mutagenesis data on the human IFN-alpha family that consists of 12 proteins. (C) 1999 Academic Pres s.