RUI: Lead interactions with metallothionein-3

在这项由化学系生命过程化学计划资助的本科生机构研究项目中，来自贝茨学院的雷切尔·N·奥斯汀博士将检验这一假设，即铅(II)与金属硫蛋白-3(MT3)结合的假说，比锌(II)与相同蛋白质结合的亲和力更大。此外，该项目将测试相关的假设，即铅(II)可以在生理相关的时间尺度上取代锌(II)，以及铅(II)饱和的MT3具有不同于锌(II)饱和的MT3的展开能量。研究将确定铅与MT3的结合亲和力，金属交换动力学，以及Zn7MT3和Pb7饱和MT3的展开温度。从这项工作中获得的定量信息将为关于MT3在铅暴露中的作用的假设提供智力基础。铅暴露，特别是在儿童时期，对发育和学习有许多深刻的影响。然而，铅进入大脑时发生的化学作用仍然知之甚少。金属硫蛋白-3是一种小的、大脑特有的蛋白质，它与其他蛋白质密切相关，这些蛋白质的功能被认为在一定程度上是与有毒金属结合以使其解毒。目前尚不清楚MT3是否在大脑中发挥这一功能，或者它是否能紧密结合铅离子。这项工作将确定铅是否真的与MT3结合，以及它是否以一种暗示这种化学物质在接触铅的生物系统中很重要的方式这样做。有关MT3和铅(II)之间的基础化学的新信息可能有助于阐明铅影响发育的生物学基础。该项目还提供了一种让本科生参与高质量研究的工具，这些研究与更广泛的社会问题有关。这个项目与以奥斯汀博士的住所为中心的社区外展活动直接重叠，该机构位于一个老磨坊小镇，那里有大量含铅的房屋库存。

In this Research at Undergraduate Institutions project, funded by the Chemistry of Life Processes Program of the Chemistry Division, Dr. Rachel N. Austin from Bates College will test the hypothesis that Pb(II) binds to metallothionein-3 (MT3), a brain specific isoform of metallothionein, with greater affinity than Zn(II) binds to the same protein. Furthermore, the project will test the correlated hypotheses that Pb(II) can displace Zn(II) on physiologically-relevant timescales and that Pb(II)-saturated MT3 has a different unfolding energy than Zn(II)-saturated MT3. Studies will determine the binding affinity of lead to MT3, the kinetics of metal exchange, and the temperature at which Zn7MT3 and Pb7-saturated MT3 unfold. Quantitative information obtained from the work will provide an intellectual foundation for hypotheses about the role of MT3 in lead exposure.Lead exposure, especially during childhood, has many profound effects on development and learning. Yet the chemistry that occurs when lead enters the brain remains poorly understood. Metallothionein-3 is a small, brain-specific protein that is closely related to other proteins whose function is understood to be, in part, to bind to toxic metals to detoxify them. It is not known whether MT3 performs this function in the brain or whether it can bind lead ions tightly. This work will determine whether lead does in fact bind to MT3 and whether it does so in a manner that would imply that this chemistry is important in biological systems exposed to lead. New information on the fundamental chemistry between MT3 and Pb(II) may help elucidate the biological basis of lead's impact on development. The project also provides a vehicle for involving undergraduate students in high-quality research that connects to larger societal concerns. This project overlaps directly with community outreach efforts centered at Dr. Austin's home institution, which is located in an old mill town with a heavy burden of lead-containing housing stock.