Crystal structure of ovine interferon-tau at 2.1 A resolution.
Crystal structure of ovine interferon-tau at 2.1 A resolution.
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DOI：
10.1006/jmbi.1998.2480
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发表时间：
1999-02
影响因子：
5.6
通讯作者：
Ramaswamy Radhakrishnan;L. J. Walter;P. Subramaniam;Howard M. Johnson;Mark R. Walter
中科院分区：
文献类型：
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作者：
Ramaswamy Radhakrishnan;L. J. Walter;P. Subramaniam;Howard M. Johnson;Mark R. Walter
绵羊干扰素-tau（ovIFN-tau）是绵羊正常胚胎发育所需的妊娠识别激素。除了其在生殖生理学中的新作用外，ovIFN-tau还显示出与IFN-α亚型相似的抗病毒和抗增殖活性。为了探索其独特活性谱的结构基础，已经在2.1 A分辨率下确定了ovIFN-tau的晶体结构。ovIFN-tau的折叠类似于先前确定的人IFN-α 2b以及人和鼠IFN-β的晶体结构，其各自含有五个α-螺旋。ovIFN-tau与huIFN-alpha 2b、huIFN-beta和muIFN-beta的比较揭示了在具有相当序列同一性的区域中发生的意想不到的结构差异。具体而言，对于螺旋A、AB环、螺旋B和BC环中的残基，出现高达11 A的主链差异。此外，已知这些区域对于受体结合和生物活性是重要的。特别令人感兴趣的是，在ovIFN-tau中观察到Glu 71和Arg 145之间的掩埋离子对，其从螺旋束核心置换保守的色氨酸残基（Trp 77）。该离子对代表了ovIFN-tau的核心与huIFN-alpha 2b相比的主要变化。基于氨基酸序列比较，这些ovIFN-tau结构特征可能在几种人IFN-α亚型和IFN-ω中是保守的。该结构确定了在解释由12种蛋白质组成的人IFN-α家族的定点诱变数据中的潜在问题。
Ovine interferon-tau (ovIFN-tau) is a pregnancy recognition hormone required for normal embryonic development in sheep. In addition to its novel role in reproductive physiology, ovIFN-tau displays antiviral and antiproliferative activities similar to the IFN-alpha subtypes. To probe the structural basis for its unique activity profile, the crystal structure of ovIFN-tau has been determined at 2.1 A resolution. The fold of ovIFN-tau is similar to the previously determined crystal structures of human IFN-alpha2b and human and murine IFN-beta, which each contain five alpha-helices. Comparison of ovIFN-tau with huIFN-alpha2b, huIFN-beta, and muIFN-beta reveals unexpected structural differences that occur in regions of considerable sequence identity. Specifically, main-chain differences up to 11 A occur for residues in helix A, the AB loop, helix B, and the BC loop. Furthermore, these regions are known to be important for receptor binding and biological activity. Of particular interest, a buried ion pair is observed in ovIFN-tau between Glu71 and Arg145 which displaces a conserved tryptophan residue (Trp77) from the helical bundle core. This ion pair represents a major change in the core of ovIFN-tau compared to huIFN-alpha2b. 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 identifies potential problems in interpreting site-directed mutagenesis data on the human IFN-alpha family that consists of 12 proteins.