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

• 批准号: 2725032
• 负责人: AMY H ANDREOTTI
• 金额: $ 11.71万
• 依托单位: IOWA STATE UNIVERSITY
• 依托单位国家: 美国
• 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/2725032
• 关键词: T lymphocyte; biological signal transduction; intermolecular interaction; nuclear magnetic resonance spectroscopy; protein structure function; protein tyrosine kinase; structural biology

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）：受监管的内部和 分子内蛋白质相互作用在信号传导中起着中心作用 控制淋巴细胞反应的事件。Itk蛋白酪氨酸 激酶是Tec家族的一员，在T细胞中起着重要的作用， 开发和激活。本研究人员以前的工作 博士后研究揭示了一种新的分子内相互作用 包括Itk中的脯氨酸残基和SH 3结构域。这里 研究人员建议根据初步的研究结果， 数据，这表明额外的调节分子内相互作用 其依赖于Itk的TH和SH 2结构域。 高分辨率多维核磁共振（NMR） 技术将被用来探索这种分子内的相互作用。 缺乏催化剂的蛋白质片段的结构和相互作用 将研究Itk的N-末端的结构域，以研究 可能调节底物结合的分子内缔合， 在完整蛋白质中的催化功能。这些研究可能提供新的 关于T和B细胞抗原信号转导的知识 受体。 此外，这些研究可能会扩大多- 三维核磁共振技术研究较大的多结构域蛋白质 系统.结合重组蛋白表达和 化学连接以产生蛋白质，其中单个结构域 同位素标记的。这项技术不仅能提供 关于Itk中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。