RUI: Copper(I) Interactions With Zinc Finger Domains

通过这一奖项，生命过程化学计划资助来自Macalester学院的Kathryn Splan教授研究铜(I)与锌指蛋白结构域的相互作用。铜(I)对硫代配体表现出很高的亲和力，这表明富含硫醇的金属蛋白结合部位，如存在于锌指结构域中的结合部位，可能会在铜浓度升高时被破坏。斯普兰教授使用光谱方法测量铜-锌指状多肽络合物的热力学稳定性和形态。本研究测试了铜(I)对锌指与DNA相互作用的影响，从而调节锌指功能的能力。这一研究结果可能有助于理解铜毒性和内稳态的机制。金属蛋白的功能与蛋白质内源性的金属离子(S)有关。用外源金属替代内源金属可能会改变蛋白质的结构和功能。斯普兰教授和Macalaster学院的本科生进行的这项研究解决了锌指蛋白中铜取代锌的问题，这可能会突显铜的毒性。在进行这项研究时，学生们接受了有关无机化学和生物学方法的培训。这些研究经验为学生提供了在许多化学和生物研究领域有用的技能，并为他们在STEM工作做好了准备。

Through this award, the Chemistry of Life Processes Program is funding Professor Kathryn Splan from Macalester College to study the interaction of copper(I) with zinc finger protein domains. Cu(I) exhibits high affinity for thiolate ligands, which suggests that thiol-rich metalloprotein binding sites such as the ones present in zinc finger domains, may be disrupted at elevated copper concentrations. Professor Splan uses spectroscopic methods to measure the thermodynamic stability- and speciation of- copper-zinc finger peptide complexes. The research tests the ability of Cu(I) to affect the interactions between zinc fingers and DNA, and thus to modulate the function of zinc fingers. The results of this research may be relevant for understanding the mechanism of copper toxicity and homeostasis.The function of metalloproteins is linked to the metal ion(s) endogenous to the protein. Substitution of the endogenous metals with exogenous ones is likely to alter the structure and function of the protein. The research conducted by Professor Splan and undergraduate students at Macalaster College addresses such a substitution of zinc by copper in a zinc finger protein, which may underline the toxic effect of copper. In conducting this research, the students are trained in methods pertaining to both inorganic chemistry and biology. The research experiences provide the students with skills useful in many areas of chemical and biological research and prepare them for careers in STEM.