Selective Copper and Iron Recognition and Sensing by Yeast Regulatory Proteins

在化学部生命过程化学项目的这一奖项中，来自芝加哥大学的川和博士将开发一套基因编码的探测器，可以监测活细胞中的铜和铁。为此，他小组一直致力于了解一组酵母调节蛋白选择性结合铜和铁的分子机制。这些蛋白质在调节铜和铁的吸收和输出方面表现出高度的敏感性和选择性，以平衡这些必需金属的细胞浓度。通过对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。这一新知识将有助于设计和开发能够选择性识别活细胞中的铜和铁并对其成像的探针。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组基因编码的铜和铁探针，可以用作了解活细胞中铜和铁的基本化学成分的工具。大约三分之一的天然蛋白质利用金属离子实现基本的生物功能。铜和铁是几乎所有生命形式所必需的，在生命系统中仔细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。这个项目的重点是了解一组蛋白质背后的确切机制，这些蛋白质可以高选择性地识别自然界中的许多其他金属离子中的铜或铁。所学到的知识将用于开发探针，使研究人员能够对活细胞中的基本金属离子进行成像。这些探针的使用将使直接观察这些金属离子在细胞内的运动和代谢以及它们在健康或患病细胞内的化学作用成为可能。该项目开发的工具可以帮助化学家和生物学家从根本上对铜和铁在生物学中的作用有新的认识。

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.