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.