STRUCTURE INVESTIGATIONS ON INTERFERON TAU

描述：（申请人摘要中的逐字记录）当前提案是 目的是了解绵羊干扰素-tau（IFNtau）的结构生物学。 这种蛋白质是最近加入的I型干扰素家族，包括 IFN α、IFN β和IFN α。它是一种20 kDa的抗亮氨酸蛋白， 在绵羊胚胎中，最初称为绵羊滋养层蛋白-I。 然而，它显示出与IFN α和IFN β的同源性。与其他干扰素一样， 绵羊IFNtau在几个方面表现出抗增殖和抗病毒活性。 物种，包括人类。然而，与其他干扰素不同， 即使在高浓度下也表现出对细胞的毒性，并且不诱导 体重减轻和骨髓抑制。因此，IFNtau是 由于其在治疗癌症方面的临床潜力， 如肾癌、毛细胞白血病、结肠肿瘤和肾肿瘤， 以及病毒感染，例如艾滋病毒、乙型肝炎和丙型肝炎。B和C型肝炎。两个独立的假设 将测试与溶液结构相关的细胞毒性和无细胞毒性 在调查过程中这项研究也可能 有助于对IFNtau信号转导机制的基础知识 在受体水平上。包括克隆在内的许多实验方法 和表达均匀15 N/13 C标记的重组蛋白， 多维核磁共振，分子模拟，圆二色谱，抗病毒 活性测定、抗增殖活性和细胞周期分析，以及 将使用细胞毒性测量。

DESCRIPTION: (Verbatim from the Applicant's Abstract) 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.