RUI: A mechanistic understanding of the impact of metal ions on the chemistry of metallothionein-3 structure and function in neuronal cells

Barnard College, New York NY

Investigators

Abstract

With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Professors Austin, Sever, and Vizcarra to study the activity of a small brain-specific protein (metallothionein-3) that has been selected because of its ability to inhibit the growth of neurons. Appropriate nerve growth is important for proper brain development. Metallothionein-3 is known to bind metal ions and the researchers hypothesize that only when it is bound to the proper compliment of metal ions does it function correctly. The team from Barnard College characterize how different metals that could be found in the brain bind to this protein, the structure of the protein when these metals are bound, and how the protein interacts with other important proteins when it is bound to these metal ions. This research gives undergraduate students at Barnard College (an all women's college) the opportunity to work on an interdisciplinary project in brain chemistry. Direct links between this research and an on-going program at Barnard College to recruit and retain talented science students from groups historically underrepresented in the sciences contribute to a college-wide effort to diversify the scientific workforce. The research in this project tests the hypothesis that metallothionein-3 (MT3), a brain specific isoform of metallothionein, tightly binds copper and that specific metallated forms of MT3 bind to actin, affecting actin polymerization. In contrast, the researchers hypothesize that when MT3 is bound to non-native metal ions like lead, it has a different structure and consequently does not facilitate the polymerization of actin. The work also probes, using neuronal cell cultures, conditions under which MT3 expression is altered. Information from this study provides new insight into MT3 function and specifically the role that metal ions play in mediating MT3's function. This research project gives undergraduate students at Barnard College (an all women's college) the opportunity to work on an interdisciplinary project in brain chemistry. Direct links between this project and an on-going program at Barnard College to recruit and retain talented science students from groups historically underrepresented in the sciences contributes to a college-wide effort to diversify the scientific workforce.