RUI: Copper(I) Interactions With Zinc Finger Domains

通过这个奖项，生命过程计划的化学资助来自麦卡莱斯特学院的凯瑟琳·斯普兰教授研究铜（I）与锌指蛋白结构域的相互作用。Cu（I）对硫醇配体表现出高亲和力，这表明富含硫醇的金属蛋白结合位点，例如存在于锌指结构域中的那些，可能在铜浓度升高时被破坏。斯普兰教授使用光谱方法来测量铜锌指肽复合物的热力学稳定性和形态。该研究测试了Cu（I）影响锌指与DNA之间的相互作用，从而调节锌指功能的能力。本研究结果对于理解铜的毒性机制和内环境稳定性具有重要意义。金属蛋白的功能与其内源性金属离子有关。 用外源金属取代内源金属可能改变蛋白质的结构和功能。由Splan教授和Macalaster学院的本科生进行的研究解决了锌指蛋白中锌被铜取代的问题，这可能强调了铜的毒性作用。 在进行这项研究时，学生接受有关无机化学和生物学方法的培训。 研究经验为学生提供了在化学和生物学研究的许多领域有用的技能，并为他们在STEM的职业生涯做好准备。

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.