STRUCTURE/FUNCTION OF HEME REGULATED EIF-2ALPHA KINASE

这项研究的长期目标是促进 了解血红蛋白合成和红细胞系的调节 在正常和异常血液学条件下的分化。 下 血红素缺乏的条件下蛋白质的合成受到抑制， 血红素调节的翻译抑制剂（HRI）的激活。 的 目前的研究重点是研究其分子机制， HRI的调节，这是维持平衡的关键 血红素和珠蛋白合成。 本提案的具体目标 （1）研究血红素调节HRI的机制， 确定血红素结合位点的数量，通过表征 血红素结合环境和通过定位血红素结合结构域。 (2)确定自身磷酸化在HRI调节中的作用 通过鉴定和突变氨基酸残基， 进行磷酸化，并通过检查这些影响， HRI功能的突变。

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.