Selective Copper and Iron Recognition and Sensing by Yeast Regulatory Proteins

University Of Chicago, Chicago IL

Investigators

Abstract

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.