RIG: Biophysical Characterization of Cdc42Hs Forms Associated with Cell Transformation

本项目将研究Cdc42Hs形式的结构和动力学及其影响细胞正常信号传导和增殖过程的能力。Cdc42Hs是Rho gtp结合信号转导蛋白Ras超家族的成员，与鸟嘌呤核苷酸结合，在多种信号转导途径中起分子定时开关作用。Cdc42Hs和其他Ras蛋白的突变已被证明可导致不受控制的细胞增殖。本项目将利用Cdc42Hs的各种缺失突变体来确定突变对该蛋白构象的影响及其与效应器结合的能力，以便更好地了解Cdc42Hs的变化及其与调节因子的相互作用影响各种重要信号转导途径的过程。核磁共振和荧光光谱将被用作表征Cdc42Hs载子形式的结构和动力学效应的工具。亚当斯博士之前已经描述了野生型Cdc42Hs，并将使用类似的分析工具来研究突变形式。更广泛的影响：人们相信这些Cdc42Hs结构和分子特征将对社会具有广泛的重要性，因为它提供了对蛋白质结构和灵活性在促进蛋白-蛋白相互作用、调节细胞信号传导和细胞间通信中的作用的基本理解。也许这个项目最重要的影响是，它将允许一个未被充分代表的少数民族研究者第一次开发一个独立的研究项目。基本结果将呈现给高年级本科生和研究生，为研究者提供与学生互动和培训的机会。分配给该项目的时间将允许研究者培养/指导技能，因为它们与促进未被充分代表的少数民族参与科学有关。研究者将在康奈尔大学艺术与科学学院少数民族特殊教育项目委员会（COSEP）等项目中与对科学感兴趣的少数民族本科生进行互动，研究者过去曾在这些项目中与少数民族学生交谈。这段时间还将用于通过参与科学会议（如生物物理学会和蛋白质学会），特别是与每个学会的少数民族事务委员会，与其他更成熟的少数民族科学家建立网络。

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.