CAREER: Evolution of Signaling Mechanisms in Membrane Receptors

职业：膜受体信号机制的进化

• 批准号: 0449117
• 负责人: Judith Klein
• 金额: --
• 依托单位: University of Pittsburgh
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-15 至 2011-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0449117&HistoricalAwards=false
• 关键词: CAREER; Evolution; Signaling; Mechanisms; Membrane

Many biomedical processes and targets involve membrane proteins (MPs) which constitute approximately 25% of the genes in typical genomes. Since MPs are in part accessible through the outside of cells, they form an important group of proteins for potential bioengineering applications. Advancing the fundamental understanding of folding and function of MPs required for such applications is a challenge that has lagged behind that of soluble proteins for many years. Intellectual Merit.The PI proposes that microbial sensory rhodopsin has evolved into eukaryotic rhodopsin through gradual replacement of the importance of helix-helix contacts with long-range contacts to form the folded receptor in order to achieve signaling capabilities within a single receptor. It is the goal of this proposal to test this hypothesis.The PI proposes that tertiary contacts between amino acids from both helical and loop regions take place during the very early stages before the helices have formed and possibly during their association. The two-stage hypothesis was based on experimental studies of bacteriorhodopsin. Broader Impact. Advancing the understanding of signaling mechanisms in membrane receptors may provide novel ways to engineer their function.This would be important for potential uses such as:-nanobiotechnology,bioengineering or medical intervention.-useful framework to integrate study of the fundamental processes folding and signal transduction -support education of and collaboration between researchers and students with disparate backgrounds in existing courses at the University of Pittsburgh-undergraduate student and (3) with high-school students summer camp in the PIs laboratory -Create a module for SAMS (Summer Academy for Minority Students) at Carnegie Mellon University where I hold a secondary appointment. -As the Chair of the Young Protein Scientists Committee of the Protein Society, I will be able to encourage future student chapters at Universities throughout the United States and Europe to engage in similar outreach activities.

许多生物医学过程和靶标都涉及膜蛋白（MPS），这些膜蛋白（MPS）约占典型基因组中约25％的基因。由于MPS可以部分通过细胞外部访问，因此它们形成了潜在生物工程应用的重要蛋白质。推进对此类应用所需的MPS折叠和功能的基本理解是一个挑战，落后于可溶性蛋白多年。 PI提出，微生物感觉视紫红质通过逐渐替换具有长距离接触的螺旋螺旋接触的重要性，以形成折叠受体，以形成折叠的受体，以在单个受体中实现信号能力，从而进化为真核视紫红质。该提案的目的是检验该假设。PI提出，在螺旋和螺旋形成之前的早期阶段，螺旋和环区域之间的氨基酸之间的三级接触发生在其相关性期间。两阶段的假设基于细菌紫红素的实验研究。更广泛的影响。促进对膜受体信号传导机制的理解可能会提供新颖的方法来设计其功能。对于潜在用途，例如： - 纳纳身体技术，生物工程或医学干预。可利用的框架以整合基本过程的折叠和信号转导的基本过程的研究 - 与研究者之间的协作 - 与跨学生之间的协作，并在跨学生之间进行了挑战，这是在跨学院的范围内的阶段性教育。匹兹堡大学生和（3）与PIS实验室的高中生夏令营 - 在卡内基·梅隆大学（Carnegie Mellon University）为SAMS（Summer Academy for Minors学生）创建一个模块，我在那里任命次要任命。 - 作为蛋白质学会的年轻蛋白质科学家委员会主席，我将能够鼓励美国和欧洲大学的未来学生章节从事类似的外展活动。