STRUCTURE/FUNCTION OF HEME REGULATED EIF-2ALPHA KINASE

这项研究的长期目标是为 对血红蛋白合成与红系调节的认识 在正常和异常血液学条件下的鉴别。在……下面 血红素缺乏的蛋白质合成受到抑制的条件是 激活血红素调节的翻译抑制物(HRI)。这个 目前的研究重点是对其分子机制的研究。 对HRI的监管是维持平衡的关键 血红素和珠蛋白的合成。这项建议的具体目的 主要内容有：(1)研究血红素对HRI的调节机制。 确定血红素结合位点的数量，通过表征 通过对血红素结合域的定位，实现了对血红素结合域的定位。 (2)确定自磷酸化在调节HRI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.