Selective Copper and Iron Recognition and Sensing by Yeast Regulatory Proteins

在这个来自化学系生命过程化学项目的奖项中，来自芝加哥大学的川和博士将开发一套基因编码探针，可以监测活细胞中的铜和铁。为此，他的小组一直致力于了解一组酵母调节蛋白的选择性铜和铁结合的分子机制。这些蛋白质在调节铜和铁的吸收和输出方面表现出高灵敏度和选择性，以平衡这些必需金属的细胞浓度。通过这些蛋白质的生化和结构表征，He小组计划揭示金属选择性的潜在机制。这些新知识将有助于设计和开发能够选择性识别和成像活细胞中铜和铁的探针。将进行进一步的蛋白质工程以增加探针的动态范围。这项研究计划的成功将提供第一套基因编码的铜和铁探针，可用作了解活细胞中铜和铁的基本化学的工具。大约三分之一的天然蛋白质利用金属离子来实现基本的生物功能。铜和铁对几乎所有的生命形式都是必不可少的，在生命系统中小心平衡这些离子对于在满足生理需求的同时避免潜在的毒性至关重要。该项目的重点是了解一组蛋白质的确切机制，这些蛋白质可以在自然界中的许多其他金属离子中高选择性地识别铜或铁。所学到的知识将用于开发探针，使研究人员能够成像活细胞中的基本金属离子。这些探针的可用性将使这些金属离子的细胞内运动和代谢及其在健康或患病细胞内的化学性质的直接可视化成为可能。该项目开发的工具可以帮助化学家和生物学家对铜和铁在生物学中的作用获得基本的新见解。

In this award from the Chemistry of Life Processes Program in the Division of Chemistry, Dr. Chuan He, from the University of Chicago, will develop a set of genetically encoded probes that can monitor copper and iron in live cells. To this end the He group has been working on understanding the molecular mechanisms of selective copper- and iron-binding by a group of yeast regulatory proteins. These proteins exhibit high sensitivity and selectivity in regulating the uptake and export of copper and iron in order to balance cellular concentrations of these essential metals. Through biochemical and structural characterization of these proteins, the He group plans to reveal the underlying mechanisms of metal selectivity. The new knowledge will aid the design and development of probes that can selectively recognize and image copper and iron in live cells. Further protein engineering will be performed to increase the dynamic range of the probes. The success of this research program will provide the first sets of genetically encoded copper and iron probes that can be used as tools for understanding the fundamental chemistry of copper and iron in live cells. Approximately one third of naturally occurring proteins utilize metal ions for essential biological functions. Copper and iron are essential for almost all life forms, and careful balance of these ions in living systems is crucial to avoid potential toxicity while satisfying physiological needs. This project focuses on understanding the exact mechanisms underlying a group of proteins that can recognize copper or iron with high selectivity among many other metal ions in nature. The knowledge learned will be used to develop probes that allow researchers to image essential metal ions in live cells. The availability of these probes will make possible direct visualization of the intracellular movement and metabolism of these metal ions and their chemistry inside healthy or diseased cells. The tools developed in this project could help chemists and biologists gain fundamental new insight into the roles of copper and iron in biology.