RUI: Lead interactions with metallothionein-3

在这个由化学学部生命过程化学项目资助的本科院校研究项目中，来自贝茨学院的Rachel N. Austin博士将测试铅（II）与金属硫蛋白-3 （MT3）结合的假设，金属硫蛋白是一种大脑特异性的金属硫蛋白异构体，与锌（II）结合在同一蛋白质上的亲和力更大。此外，该项目将测试相关假设，即Pb（II）可以在生理相关的时间尺度上取代Zn(II), Pb（II）饱和MT3的展开能量与Zn（II）饱和MT3的展开能量不同。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展开的温度。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知识基础。铅接触，特别是在儿童时期，对发育和学习有许多深远的影响。然而，当铅进入大脑时发生的化学反应仍然知之甚少。金属硫蛋白-3是一种小的脑特异性蛋白质，与其他蛋白质密切相关，其功能被认为是部分地与有毒金属结合以解毒。目前尚不清楚MT3是否在大脑中发挥这一功能，也不知道它是否能将铅离子紧密结合。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作用在暴露于铅的生物系统中很重要的方式结合。关于MT3和Pb（II）之间基本化学关系的新信息可能有助于阐明铅对发育影响的生物学基础。该项目还提供了一个工具，让本科生参与高质量的研究，这些研究与更大的社会问题有关。该项目直接与Austin博士的家庭机构的社区外展工作重叠，该机构位于一个古老的磨坊镇，那里有沉重的含铅住房负担。

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.