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: 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
• 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

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（根据调查人员的摘要改编）：受监管的间和 分子内蛋白质相互作用在信号中起着核心作用 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细胞中起重要作用 开发和激活。该调查人员的先前工作 博士后研究揭示了一种新型分子内相互作用 ITK中涉及脯氨酸残基和SH3域。在这里， 研究者建议根据初步扩展这些研究 数据，这表明其他分子内相互作用 取决于ITK的TH和SH2域。 高分辨率多维核磁共振（NMR） 技术将用于探索这种分子内相互作用。 缺乏催化性的蛋白质片段的结构和相互作用 将研究ITK N末端的域以研究 分子内关联可能调节底物结合和 完整蛋白质中的催化功能。这些研究可能会提供新的 关于T和B细胞抗原信号转导信号的知识 受体。 此外，这些研究可能会扩大多种多样的应用 较大多域蛋白的研究尺寸NMR技术 系统。新型技术结合重组蛋白表达和 化学连接生成单个域的蛋白质 提出了同位素标记。这项技术不仅会提供 有关ITK中分子内相互作用的详细信息，但会 广泛适用于研究中分子内相互作用 其他具有复杂结构域结构的蛋白质。