Directional copper trafficking: In vitro and in vivo studies of metal binding and transfer

定向铜运输：金属结合和转移的体外和体内研究

• 批准号: BB/E016529/1
• 负责人: Christopher Dennison
• 金额: $ 60.32万
• 依托单位: Newcastle University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FE016529%2F1
• 关键词: Directional; copper; trafficking; vitro; vivo

A protein is a biological polymer with a complex three-dimensional structure. Many proteins bind metal ions which are usually essential for both structure and function even though the metals constitute typically less than 0.5 % of the total mass of the molecule (approximately one third of all proteins contain metals and these molecules are called metalloproteins). Metal ions have to be incorporated into the correct proteins within cells, and systems (networks of proteins) are emerging via which this is achieved. These regulatory networks of proteins also prevent the potentially damaging effects of the uncontrolled reactivity of metal ions and when these systems are impaired various diseases can result. The proposed studies aim to investigate the proteins which are responsible for ensuring that copper is supplied to the correct destination in a relatively simple model organism. Metal affinities of all of the proteins involved will be determined as will their ability to transfer copper. The effects of designed alterations to the protein structure on metal binding and transfer, protein interactions as well as the influence on physiological activity in the model organism will all be assessed. A detailed appreciation of the factors regulating this important biological process will be obtained.

蛋白质是具有复杂三维结构的生物聚合物。许多蛋白质结合金属离子，这些金属离子通常对结构和功能都是必不可少的，即使金属通常占分子总质量的不到0.5%（大约三分之一的蛋白质含有金属，这些分子被称为金属蛋白质）。金属离子必须被整合到细胞内的正确蛋白质中，而系统（蛋白质网络）正在出现，通过它来实现这一点。这些蛋白质的调节网络还防止金属离子的不受控制的反应性的潜在破坏性影响，并且当这些系统受损时，可能导致各种疾病。拟议的研究旨在研究负责确保铜在相对简单的模式生物中被供应到正确目的地的蛋白质。所有涉及的蛋白质的金属亲和力将被确定，因为它们转移铜的能力。将评估蛋白质结构的设计改变对金属结合和转移、蛋白质相互作用的影响以及对模型生物体中生理活性的影响。调节这一重要的生物过程的因素的详细评价将获得。

项目成果

Crosstalk between Cu(I) and Zn(II) homeostasis via Atx1 and cognate domains.

• DOI: 10.1039/c3cc42709a
• 发表时间: 2013-09-21
• 期刊: Chemical communications (Cambridge, England)
• 作者: Badarau A;Baslé A;Firbank SJ;Dennison C
• 通讯作者: Dennison C