STRUCTURE/FUNCTION OF HEME REGULATED EIF-2ALPHA KINASE

血红素调节的 EIF-2α 激酶的结构/功能

• 批准号: 2905157
• 负责人: MARYAM RAFIE-KOLPIN
• 金额: $ 3.67万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-06-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2905157
• 关键词: enzyme activity; enzyme mechanism; genetic translation; heme; mass spectrometry; protein binding; protein kinase; protein sequence; protein structure function; translation factor; western blottings

The long term objective of this research is to contribute to the understanding of the regulation of hemoglobin synthesis and erythroid differentiation in normal and abnormal hematologic conditions. Under conditions of heme deficiency protein synthesis is inhibited due to activation of the heme regulated translational inhibitor (HRI). The focus of the current research is to study the molecular mechanisms in the regulation of HRI which are critical in maintaining the balanced synthesis of heme and globin. The specific aims of this proposal are: (1) Examine the mechanism of heme regulation of HRI by identifying the number of heme-binding sites, by characterizing the heme-binding environment and by localizing the heme -binding domains. (2) Determine the role of autophosphrylation in the regulation of HRI by identification and mutation of the amino acid residues that undergo phosphorylation, and by examination of the effects of these mutations on the function of HRI.

这项研究的长期目标是为 了解血红蛋白合成和红细胞的调节 区分正常和异常血液学状况。 在下面 血红素缺乏的情况下蛋白质合成受到抑制 血红素调节翻译抑制剂（HRI）的激活。 这 目前研究的重点是研究其分子机制 HRI 的监管对于维持平衡至关重要 血红素和珠蛋白的合成。 本提案的具体目标 是： (1) 通过以下方法研究血红素对 HRI 的调节机制： 通过表征来确定血红素结合位点的数量 血红素结合环境并通过本地化血红素结合域。 (2)确定自磷酸化在HRI调节中的作用 通过氨基酸残基的鉴定和突变 进行磷酸化，并通过检查这些作用 HRI 功能的突变。