A Three-Dimensional Model of Interferon-τ

Abstract

The interferon-τ(IFN-τ) are type IIFN whose expression is restricted to the embryonic trophectoderm of the developing placenta of ruminant ungulate species, where they act as hormones of pregnancy. Here computer modeling has been used to generate homology models of bovine and ovine IFN-τ based on the refined crystal structure of murine IFN-β. The IFN-τ structure, like that of MuIFN-β, is based on five long α helices (A-E), one short helix in the middle of the loop connecting helices C and D and a long loop between helices A and B. BoIFN-τ differs from MuIFN-β in three important respects. First, as in all IFN-τ, there is a carboxyl tail of nine amino acids that cannot be accurately modeled but that would have a length of ∼30 Å when fully extended. Second, like the IFN-α subtype, all IFN-τ have a three-amino acid insertion in loop AB and a likely disulfide bridge between Cys29 and Cys139 that lead to marked conformational differences between them and MuIFN-β in a region (Leu22 to Arg33 in IFN-τ) believed to interact with the receptor. Third, all IFN-τ, as well as the related IFN-ω, possess a Gly at position 126 (rather than the equivalent Arg on MuIFN-β and IFN-α) 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 Gln40) of loop AB is likely to be considerably more flexible than in other type I IFN.