Structural Studies of Transcriptional Regulators

转录调节因子的结构研究

• 批准号: 6573277
• 负责人: MITCHELL LEWIS
• 金额: $ 31.35万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-07-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6573277
• 关键词: SDS polyacrylamide gel electrophoresis; crystallization; gene induction /repression; genetic regulation; genetic transcription; lac operon; lactose; polymerase chain reaction; protein structure function; structural biology; transcription factor

DESCRIPTION (provided by applicant): The long-range goal of our research is to understand the structural basis of gene regulation and how repressors, activators, and anti-terminators regulate transcription. Over the years, we have focused on the two paradigms, the lactose operon of E-coli and the "genetic switch" of bacteriophage lambda. This grant originally funded the three-dimensional structure determination of the intact lac repressor, the lac repressor bound to the gratuitous inducer 1-isopropyl-D-thiogalactoside (IPTG) and the lac repressor complexed with a 21 base-pair symmetric operator DNA. These three structures have provided a detailed structural model for repressor in the induced and the repressed states, and a framework for understanding a wealth of biochemical and genetic information (Lewis et al., 1996). Building upon these results, we designed new experiments and solved structures to probe more deeply the function of this protein. In this last granting period, we also resumed earlier studies of the repressor from phage lambda (Bell et al., 2000) and provided structural insight as to the molecular basis of this genetic switch. In this funding period, we plan to continue our studies on proteins that regulate transcription. The long-range goal of our research is to understand the structural basis of gene regulation and how repressors, activators, and anti-terminators regulate transcription.

描述(由申请人提供)：我们研究的长期目标是了解基因调控的结构基础，以及抑制物、激活物和反终止物如何调控转录。多年来，我们一直专注于两个范例，即大肠杆菌的乳糖操纵子和噬菌体lambda的“遗传开关”。这笔资金最初用于完整的lac抑制物、与无偿诱导物1-异丙基-D-硫代半乳糖苷(IPTG)结合的lac抑制物和与21个碱基对的对称操纵子DNA复合的lac抑制物的三维结构测定。这三种结构为阻遏子在诱导和抑制状态下的结构提供了一个详细的模型，并为理解丰富的生化和遗传信息提供了一个框架(Lewis等人，1996)。在这些结果的基础上，我们设计了新的实验和解决了结构，以更深入地探索该蛋白质的功能。在这最后一次授予期间，我们还恢复了对噬菌体lambda抑制子的早期研究(Bell等人，2000年)，并提供了关于这种遗传开关的分子基础的结构洞察力。在这一资助期间，我们计划继续我们对调节转录的蛋白质的研究。我们研究的长期目标是了解基因调控的结构基础，以及抑制子、激活子和反终止子如何调控转录。