STRUCTURAL STUDIES OF INTERFERON GAMMA RECEPTOR COMPLEX

描述：该提案的目标是了解结构 细胞因子通过其受体特异性识别的基础。 的 干扰素-q（IFN-q）及其与 中和Fab片段以及细胞外片段 两种重组人干扰素-Q受体的研究正在进行中。 所有形式的IFN-q的原子坐标的比较将阐明 与受体结合时发生的构象变化。 理解诱导抗- IFN-q的病毒和细胞抑制特性对于设计 调节其活性的分子。将尝试使用 设计和测试肽模拟物或人源化Fab的结构结果 IFN-q的拮抗剂。 IFN-q拮抗剂可能具有治疗价值 治疗自身免疫性疾病、慢性炎症和 同种异体移植排斥反应。 已经提供了大量的初步数据 表明所提出的目标是可行的。

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.