STRUCTURAL STUDIES OF A T CELL SPECIFIC TYROSINE KINASE

T 细胞特异性酪氨酸激酶的结构研究

基本信息

批准号：
6137270
负责人：
AMY H ANDREOTTI
金额：
$ 13.57万
依托单位：
IOWA STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-01-15 至 2003-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6137270
关键词：
T lymphocyte biological signal transduction intermolecular interaction nuclear magnetic resonance spectroscopy protein structure function protein tyrosine kinase structural biology

项目摘要

DESCRIPTION (Adapted from Investigators Abstract): Regulated inter- and intramolecular protein interactions play central roles in signaling events that control lymphocytes responses. The Itk protein tyrosine kinase, a member of the Tec family, plays an important role in T cell development and activation. Previous work from this investigators postdoctoral studies revealed a novel intramolecular interaction involving proline residues and the SH3 domain in Itk. Here, the investigator proposes to extend those studies, based on preliminary data, that suggest additional regulatory intramolecular interactions which depend upon the TH and SH2 domain of Itk. High resolution multidimensional nuclear magnetic resonance (NMR) techniques will be used to explore this intramolecular interaction. Structures and interactions of protein fragments lacking the catalytic domain of the N-terminus of Itk will be studied to investigate the intramolecular associations that might regulate substrate binding and catalytic function in the intact protein. These studies may provide new knowledge regarding signal transduction by T and B cell antigen receptors. Furthermore, these studies may broaden the application of multi- dimensional NMR techniques to the study of larger multi-domain protein systems. Novel techniques combining recombinant protein expression and chemical ligation to generate proteins in which a single domain is isotopically labeled are proposed. This technology will not only provide detailed information about intramolecular interactions in Itk, but will be broadly applicable to the study of intramolecular interactions in other protein with complex domain structure.

描述（改编自研究者摘要）：受监管的国际和分子内蛋白质相互作用在信号传导中发挥核心作用控制淋巴细胞反应的事件。 Itk 蛋白酪氨酸激酶是 Tec 家族的成员，在 T 细胞中发挥着重要作用开发和激活。该研究人员之前的工作博士后研究揭示了一种新的分子内相互作用涉及脯氨酸残基和 Itk 中的 SH3 结构域。在这里，研究人员建议根据初步结果扩大这些研究数据表明额外的分子内调节相互作用这取决于 Itk 的 TH 和 SH2 结构域。高分辨率多维核磁共振 (NMR) 将使用技术来探索这种分子内相互作用。缺乏催化的蛋白质片段的结构和相互作用将研究 Itk N 末端的结构域以调查可能调节底物结合的分子内关联和完整蛋白质中的催化功能。这些研究可能提供新的有关 T 细胞和 B 细胞抗原信号转导的知识受体。此外，这些研究可能会拓宽多学科的应用。三维核磁共振技术研究更大的多结构域蛋白质系统。结合重组蛋白表达和化学连接产生具有单个结构域的蛋白质建议采用同位素标记。这项技术不仅将提供 Itk 中有关分子内相互作用的详细信息，但将广泛适用于分子内相互作用的研究其他具有复杂结构域的蛋白质。