The current proposal is aimed at understanding the structural biology of ovine interferon-tau (IFNtau). This protein is a recent addition to the type I interferon family that includes IFNalpha IFNbeta, and IFNalpha. It is a 20 kDa antileuteolitic protein produced in sheep conceptuses, and originally called ovine trophoblast protein-I. However, it shows homology to IFNalpha and IFNbeta. Like other interferons, ovine IFNtau exhibits antiproliferative and antiviral activities across several species, including humans. Unlike other interferons, however, it does not exhibit toxicity to cells even at high concentrations, and does not induce weight loss and bone marrow suppression in animal models. Thus IFNtau is of considerable interest because of its clinical potential in treating cancers such as renal carcinoma, hairy cell leukemia, colon tumors, and kidney tumors, and viral infections such as HIV and hepatitis B and C. Two separate hypotheses relating to the solution structure and lack of cytotoxicity will be tested during the course of this investigation. This study is also likely to contribute to basic knowledge on the mechanism of signal transduction by IFNtau at the level of receptor. A number of experimental methods that include cloning and expression of uniformly 15N/13C-labeled recombinant proteins, multidimensional NMR, molecular modeling, circular dichroism, antiviral activity assay, antiproliferative activity and cell cycle analyses, and cytoxicity measurements will be used.
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