STRUCTURAL STUDIES OF INTERFERON GAMMA RECEPTOR COMPLEX

描述：该提案的目标是了解结构 细胞因子受体特异性识别细胞因子的基础。这个 干扰素-Q及其配合物的结晶学研究 中和Fab片段以及与胞外片段 两种重组人干扰素-Q受体中的一种正在进行中。 比较所有形式的干扰素-Q的原子坐标将阐明 当与受体结合时发生的构象变化。 了解结构识别机制，诱导抗- 干扰素-Q的病毒和细胞抑制特性是设计的关键 调节其活性的分子。将尝试使用 设计和测试模拟多肽或人源化Fab的结构结果 干扰素-Q拮抗剂。干扰素-Q拮抗剂可能具有治疗价值 在治疗自身免疫性疾病方面，慢性炎症和 同种异体排斥反应。已经提供了大量的初步数据 以表明所宣布的目标是可行的。

DESCRIPTION: The goal of the proposal is to understand the structural basis for the specific recognition of cytokines by their receptors. The crystallographic studies of interferon-q (IFN-q) and its complexes with a neutralizing Fab fragment as well as with the extracellular fragments of the two recombinant human interferon-q receptors are in progress. Comparison of the atomic coordinates of all forms of IFN-q will elucidate the conformational changes that occur upon binding to the receptor. Understanding the structural recognition mechanisms that induce the anti- viral and cytostatic properties of IFN-q is critical for designing molecules which modulate its activity. Attempts will be made to use the structural results to design and test peptidomimetics or humanized Fab antagonists of IFN-q. Antagonists of IFN-q may have therapeutic value in the treatment of autoimmune diseases, chronic inflammation and allograft rejection. Substantial preliminary data have been presented to suggest that the stated goals are feasible.