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

有了这个奖项，化学学部的生命过程化学项目将资助Austin、Sever和Vizcarra教授研究一种脑特异性小蛋白（金属硫蛋白-3）的活性，这种蛋白之所以被选中，是因为它具有抑制神经元生长的能力。神经的正常生长对大脑的正常发育很重要。已知金属硫蛋白-3与金属离子结合，研究人员假设，只有当它与适当的金属离子结合时，它才能正常发挥作用。巴纳德学院的研究小组描述了大脑中发现的不同金属是如何与这种蛋白质结合的，这些金属结合时蛋白质的结构，以及当蛋白质与这些金属离子结合时蛋白质是如何与其他重要蛋白质相互作用的。这项研究为巴纳德学院（一所女子学院）的本科生提供了一个参与脑化学跨学科项目的机会。这项研究与巴纳德学院（Barnard College）正在进行的一项计划之间的直接联系，该计划旨在从历史上在科学领域代表性不足的群体中招募和留住有才华的理科生，这有助于全校范围内努力使科学劳动力多样化。本项目的研究验证了金属硫蛋白-3 (metallothionein-3, MT3)，一种脑特异性金属硫蛋白异构体，与铜紧密结合的假设，以及特定金属化形式的MT3与肌动蛋白结合，影响肌动蛋白聚合的假设。相反，研究人员假设，当MT3与非天然金属离子（如铅）结合时，它具有不同的结构，因此不能促进肌动蛋白的聚合。这项工作还利用神经细胞培养，探索了MT3表达改变的条件。这项研究的信息为MT3的功能提供了新的见解，特别是金属离子在介导MT3功能中的作用。这个研究项目为巴纳德学院（一所女子学院）的本科生提供了一个从事脑化学跨学科项目的机会。该项目与巴纳德学院（Barnard College）正在进行的从历史上在科学领域代表性不足的群体中招募和留住有才华的理科生的项目之间的直接联系，有助于全校范围内的科学劳动力多样化努力。

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.