Copper is a redox–active transition metal ion required for the function of many essential human proteins. For biosynthesis of proteins coordinating copper, the metal may bind before, during or after folding of the polypeptide. If the metal binds to unfolded or partially folded structures of the protein, such coordination may modulate the folding reaction. The molecular understanding of how copper is incorporated into proteins requires descriptions of chemical, thermodynamic, kinetic and structural parameters involved in the formation of protein–metal complexes. Because free copper ions are toxic, living systems have elaborate copper-transport systems that include particular proteins that facilitate efficient and specific delivery of copper ions to target proteins. Therefore, these pathways become an integral part of copper protein folding in vivo. This review summarizes biophysical-molecular in vitro work assessing the role of copper in folding and stability of copper-binding proteins as well as protein–protein copper exchange reactions between human copper transport proteins. We also describe some recent findings about the participation of copper ions and copper proteins in protein misfolding and aggregation reactions in vitro.

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铜蛋白的折叠：金属的作用？

铜是一种具有氧化还原活性的过渡金属离子，是许多人体必需蛋白质的功能所必需的。对于与铜配位的蛋白质的生物合成，金属可以在多肽折叠之前、期间或之后结合。如果金属与蛋白质的未折叠或部分折叠结构结合，则这种配位可能会调节折叠反应。对铜如何掺入蛋白质的分子理解需要描述与蛋白质-金属复合物形成有关的化学、热力学、动力学和结构参数。因为游离铜离子是有毒的，所以生命系统具有复杂的铜转运系统，其中包括特定的蛋白质，这些蛋白质有助于将铜离子有效和特异性地输送到目标蛋白质。因此，这些途径成为铜蛋白折叠的组成部分体内. 这篇综述总结了生物物理-分子体外工作评估铜在铜结合蛋白的折叠和稳定性以及人类铜转运蛋白之间的蛋白质-蛋白质铜交换反应中的作用。我们还描述了一些关于铜离子和铜蛋白参与蛋白质错误折叠和聚集反应的最新发现体外.