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

RUI：金属离子对神经元细胞中金属硫蛋白-3 结构和功能的化学影响的机制理解

• 批准号: 1710176
• 负责人: Christina Vizcarra
• 金额: $ 29.4万
• 依托单位: Barnard College
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1710176&HistoricalAwards=false
• 关键词: RUI; mechanistic; understanding; impact; metal

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.

通过这个奖项，化学系的生命过程化学项目资助Austin、Sever和Vizcarra教授研究一种大脑特有的小蛋白(金属硫蛋白-3)的活性，这种蛋白之所以被选中，是因为它有能力抑制神经元的生长。适当的神经生长对大脑的正常发育很重要。众所周知，金属硫蛋白-3可以与金属离子结合，研究人员推测，只有当它与金属离子的适当补充结合时，它才能正常发挥作用。来自巴纳德学院的团队表征了大脑中发现的不同金属如何与这种蛋白质结合，当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，蛋白质如何与其他重要蛋白质相互作用。这项研究为巴纳德学院(一所女子学院)的本科生提供了从事脑化学跨学科项目的机会。这项研究与巴纳德学院正在进行的一个项目之间的直接联系，该项目旨在从历史上在科学界代表性较低的群体中招聘和留住有才华的理科学生，这有助于整个学院努力使科学队伍多样化。该项目的研究验证了一种假说，即大脑中金属硫蛋白的一种特定亚型金属硫蛋白-3(MT3)与铜紧密结合，而特定金属形式的MT3与肌动蛋白结合，影响肌动蛋白聚合。相反，研究人员假设，当MT3与铅等非天然金属离子结合时，它具有不同的结构，因此不利于肌动蛋白的聚合。这项工作还利用神经细胞培养来探索MT3表达发生变化的条件。本研究提供了对MT3功能的新认识，特别是金属离子在介导MT3‘S功能中所起的作用。这项研究项目为巴纳德学院(一所女子学院)的本科生提供了从事脑化学跨学科项目的机会。该项目与巴纳德学院正在进行的一个项目之间的直接联系，该项目旨在从历来在科学界代表性较低的群体中招聘和留住有才华的理科学生，这有助于整个学院努力使科学队伍多样化。