Structural and functional characterization of protein-metal interactions.

金属结合蛋白在调节许多生物过程中起着至关重要的作用，人们对描述蛋白质-金属相互作用的机制细节很感兴趣。例如，钙、铜、铁和锌等金属通过重要的蛋白质-金属相互作用发挥着关键的生物学作用。除了它们的基本作用外，许多金属也是有毒的，因为它们能够以不利的方式结合蛋白质。对我们的健康和环境构成严重威胁的有毒金属包括汞、铅、镉和砷。在过去的二十年里，我的实验室一直在研究蛋白质与必需金属和有毒金属的相互作用。我们研究计划的长期目标是从结构和功能上表征蛋白质与必需金属和有毒金属的相互作用。特别是，我们感兴趣的是必需金属如何帮助选择蛋白质折叠成其功能构象，以及有毒金属如何扰乱正常过程。目前，实验室中正在进行几项研究，检测蛋白质-金属，包括那些在许多重要的生物过程中发挥重要作用的研究。此外，我们正在研究一些有毒金属，如汞和铅与细胞蛋白质的相互作用，以及这些相互作用如何与这些金属的毒性相关。拟议的结构和功能研究的结合将提供对于理解蛋白质-金属相互作用在金属毒性、胰岛素调节、甲基汞修复、MicroRNA调节、肿瘤抑制和抗艾滋病毒治疗中的作用至关重要的信息。

Metal-binding proteins play crucial roles in regulating a number of biological processes, and there is considerable interest in characterizing the mechanistic details of protein-metal interactions. For example, metals such as calcium, copper, iron and zinc play key biological roles through important protein-metal interactions. In addition to their essential roles, a number of metals are toxic due to their ability to bind proteins in an adverse manner. Toxic metals that pose a serious threat to both our health and environment include mercury, lead, cadmium and arsenic. For the last twenty year, my laboratory has been characterizing the interaction of proteins with both essential and toxic metals. The long-term objectives of our research program are to structurally and functionally characterize the interaction of proteins with both essential and toxic metals. In particular, we are interested in how essential metals help select proteins fold into their functional conformation as well as how toxic metals can disrupt the normal process. Currently, there are several ongoing investigations in the laboratory examining protein-metal including those that play important roles in a number of important biological processes. In addition, we are examining the interaction of a number of toxic metals such as mercury and lead with cellular proteins and how these interactions are associated with the toxicity of these metal. The proposed combination of structural and functional studies will provide information that is essential for understanding the role of protein-metal interactions in metal toxicity, insulin regulation, methylmercury remediation, microRNA regulation, tumour suppression and anti-HIV therapy.