Senda T, Saitoh S I, Mitsui Y, Li J, Roberts R M
Department of BioEngineering, Nagaoka University of Technology, Niigata, Japan.
J Interferon Cytokine Res. 1995 Dec;15(12):1053-60. doi: 10.1089/jir.1995.15.1053.
The interferon-tau (IFN-tau) are type I IFN 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-tau based on the refined crystal structure of murine IFN-beta. The IFN-tau structure, like that of MuIFN-beta, is based on five long alpha 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-tau differs from MuIFN-beta in three important respects. First, as in all IFN-tau, there is a carboxyl tail of nine amino acids that cannot be accurately modeled but that would have a length of approximately 30 A when fully extended. Second, like the IFN-alpha subtype, all IFN-tau 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-beta in a region (Leu22 to Arg33 in IFN-tau) believed to interact with the receptor. Third, all IFN-tau, as 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 Gln40) of loop AB is likely to be considerably more flexible than in other type I IFN.
干扰素 -τ（IFN-τ）属于I型干扰素，其表达仅限于反刍有蹄类动物发育中胎盘的胚胎滋养外胚层，在那里它们作为妊娠激素发挥作用。在此，基于小鼠IFN-β的精细晶体结构，利用计算机建模生成了牛和羊IFN-τ的同源模型。IFN-τ的结构与小鼠IFN-β一样，基于五个长α螺旋（A - E）、连接螺旋C和D的环中间的一个短螺旋以及螺旋A和B之间的一个长环。牛IFN-τ在三个重要方面与小鼠IFN-β不同。首先，与所有IFN-τ一样，有一个由九个氨基酸组成的羧基末端，无法精确建模，但完全伸展时长度约为30埃。其次，与IFN-α亚型一样，所有IFN-τ在环AB中有一个三个氨基酸的插入片段，并且在Cys29和Cys139之间可能存在二硫键，这导致它们与小鼠IFN-β在一个据信与受体相互作用的区域（IFN-τ中的Leu22至Arg33）存在明显的构象差异。第三，所有IFN-τ以及相关的IFN-ω在第126位都有一个甘氨酸（而不是小鼠IFN-β和IFN-α中的等效精氨酸），这将削弱螺旋D与环AB之间广泛的氢键相互作用。因此，环AB这个区域（Phe36至Gln40）周围的多肽片段可能比其他I型干扰素中的片段更加灵活。
