RIG: Biophysical Characterization of Cdc42Hs Forms Associated with Cell Transformation

该项目将研究Cdc 42 Hs形式的结构和动力学，这些形式与其影响细胞信号传导和增殖的正常过程的能力有关。Cdc 42 Hs是Rho GTP结合信号转导蛋白Ras超家族的成员，其结合鸟嘌呤核苷酸并在多个信号转导途径中充当分子定时开关。Cdc 42 H和其他Ras蛋白的突变已被证明会导致不受控制的细胞增殖。在这个项目中，各种缺失突变的Cdc 42 Hs将被用来确定这种蛋白质的构象和它的能力，结合其效应器的突变的影响，以获得更好的理解的过程中，Cdc 42 Hs的变化及其与监管机构的相互作用，影响各种重要的信号转导途径。NMR和荧光光谱将被用来作为工具，以表征Cdc 42 Hs的载脂蛋白形式的结构和动力学效应。亚当斯博士先前已经对野生型Cdc 42 Hs进行了表征，并将使用类似的分析工具来研究突变形式。 更广泛的影响：据信，这些Cdc 42 Hs构建体的结构和分子表征将通过提供对蛋白质结构和灵活性在促进调节细胞信号传导和细胞间通讯的蛋白质-蛋白质相互作用中所起作用的基本理解而对社会具有广泛的重要性。也许这个项目最重要的影响是，它将允许一个代表性不足的少数民族研究人员首次开发一个独立的研究计划。基本结果将提交给高水平的本科生和研究生，为研究人员提供与学生互动和培训的机会。分配给该项目的时间将使调查员能够发展培养/指导技能，因为这些技能与促进代表性不足的少数群体参与科学有关。调查员将与少数民族本科生在项目中对科学感兴趣，如康奈尔大学艺术与科学学院少数民族COSEP（特殊教育项目委员会）项目，其中调查员过去曾与少数民族学生交谈。这段时间还将用于通过参加生物物理学会和蛋白质学会等科学会议，特别是与每个学会的少数群体事务委员会建立与其他更有地位的少数群体科学家的网络。

This project will study the structure and dynamics of Cdc42Hs forms associated with its ability to affect the normal processes of cell signaling and proliferation. Cdc42Hs is a member of the Ras superfamily of Rho GTP-binding signal transduction proteins, which binds guanine nucleotides and acts as a molecular timing switch in multiple signal transduction pathways. Mutations in Cdc42Hs and other Ras proteins have been shown to lead to uncontrolled cell proliferation. In this project various deletion mutants of Cdc42Hs will be used to determine the effect of mutation on the conformation of this protein and its ability to bind to its effectors, in order to gain a better understanding of the processes by which changes in Cdc42Hs and its interaction with regulators affect various important signal transduction pathways. NMR and fluorescence spectroscopy will be used as tools to characterize the structural and dynamic effects of the apo form of Cdc42Hs. Dr. Adams has previously characterized the wild type Cdc42Hs and will use similar analytical tools to study the mutant forms. Broader Impacts: It is believed that the structural and molecular characterization of these Cdc42Hs constructs will have a broad importance to society by providing a basic understanding of the role that protein structure and flexibility play in facilitating protein-protein interactions that regulate cell signaling and intercellular communication. Perhaps the most important impact of this project is that it will allow an underrepresented minority investigator to develop an independent research program for the first time. The fundamental results will be presented to upper level undergraduate and graduate students, providing the investigator the chance to interact with and provide training to students. The time period allotted for this project will allow for the development of nurturing/mentoring skills by the investigator as they relate to the promotion of participation of underrepresented minorities in science. The investigator will interact with minority undergraduate students interested in science in programs such as the Cornell University College of Arts and Sciences Minority COSEP (Committee of Special Educational Projects) program, where the investigator has spoken with minority students in the past. This time will also be used to establish networks with other, more established minority scientists through involvement in scientific conferences, such as the Biophysical Society and the Protein Society, particularly with minority affairs committees for each society.