CAREER: Dissecting Signal Recognition and Allostery in Ligand-Responsive Biological Functions

职业：剖析配体响应生物功能中的信号识别和变构

• 批准号: 0953430
• 负责人: Herschel Wade
• 金额: $ 93万
• 依托单位: Johns Hopkins University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0953430&HistoricalAwards=false
• 关键词: CAREER; Dissecting; Signal; Recognition; Allostery

Intellectual MeritThe goal of this CAREER project is to understand how biological systems read and transform chemical signals into a diverse range of biological outputs. Improved descriptions of ligand-responses have implications from facilitating a general understanding of biological control to the design of regulatory systems with pre-defined activities, both of which have wide-spread uses in biomedical, engineering, environmental and biotechnological applications. How do ligand-responsive functions recognize the correct ligand structures, discriminate against incorrect ones and transform binding events into controlled responses? To better understand the functional roles of ligand interactions in regulatory systems, this project focuses on BmrR, a small molecule-sensing gene regulator whose activity is stimulated by a number of chemically diverse small-molecules. In the described work, biochemical, biophysical and X-ray crystallographic approaches are employed to dissect and examine ligand-directed effects at the binding, functional and structural levels. The aim is to combine functional, thermodynamic and structural studies into a more integrative analysis of ligand recognition and ligand-dependent control of protein conformation. Broader ImpactThe broader impacts involve better connecting underrepresented minorities with the biological and physical science communities through mechanisms that target students at the elementary, high school and undergraduate levels. At the elementary and high school levels, these plans include continued involvement in Baltimore-based programs in which students and teachers in the area participate in science-based discussions, demonstrations and hands-on activities. The integrated research and educational plans focus on increasing the participation of underrepresented minorities in basic science research and providing training opportunities for elementary, high school and graduate students.

这个职业生涯项目的目标是了解生物系统如何读取和转换化学信号到各种生物输出。 改进的配体反应的描述具有从促进对生物控制的一般理解到具有预定义活动的调节系统的设计的影响，这两者在生物医学、工程、环境和生物技术应用中具有广泛的用途。 配体反应功能如何识别正确的配体结构，区分不正确的配体结构，并将结合事件转化为受控反应？ 为了更好地了解配体相互作用在调控系统中的功能作用，该项目的重点是BmrR，一种小分子传感基因调控因子，其活性受到许多化学上不同的小分子的刺激。 在所描述的工作中，生物化学，生物物理学和X射线晶体学方法被用来解剖和检查配体定向的结合，功能和结构水平的影响。 其目的是将联合收割机功能、热力学和结构研究结合到配体识别和蛋白质构象的配体依赖性控制的更综合的分析中。 更广泛的影响更广泛的影响涉及通过针对小学、高中和大学生的机制，更好地将代表性不足的少数群体与生物和物理科学界联系起来。 在小学和高中一级，这些计划包括继续参与巴尔的摩的项目，该地区的学生和教师参加以科学为基础的讨论、示范和实践活动。 综合研究和教育计划的重点是增加代表性不足的少数群体对基础科学研究的参与，并为小学、高中和研究生提供培训机会。