A 3-DIMENSIONAL MODEL OF INTERFERON-TAU

The interferon-tau(IFN-tau) are type I IFN whose expression is restric ted to the embryonic trophectoderm of the developing placenta of rumin ant ungulate species, where they act as hormones of pregnancy, Here co mputer modeling has been used to generate homology models of bovine an d ovine IFN-tau based on the refined crystal structure of murine IFN-b eta. The IFN-tau structure, like that of MuIFN-beta, is based on five long a helices (A-E), one short helix in the middle of the loop connec ting helices C and D and a long loop between helices A and B, BoIFN-ta u differs from MuIFN-beta in three important respects, First, as in al l IFN-tau, there is a carboxyl tail of nine amino acids that cannot be accurately modeled but that would have a length of similar to 30 Angs trom when fully extended, Second, like the IFN-alpha subtype, all IFN- tau have a three-amino acid insertion in loop AB and a likely disulfid e bridge between Cys29 and Cys139 that lead to marked conformational d ifferences between them and MuIFN-beta in a region (Leu22 to Arg33 in IFN-tau) believed to interact with the receptor, Third, all IFN-tau, a s well as the related IFN-omega, possess a Gly at position 126 (rather than the equivalent Arg on MuIFN-beta and IFN-alpha) that will impair an extensive hydrogen bonding interaction between helix D and loop AB , As a result, the polypeptide segment around this region (Phe36 to Gl n40) of loop AB is likely to be considerably more flexible than in oth er type IIFN.