Copper plays a vital role in fundamental cellular functions, and its concentration in the cell must be tightly regulated, as dysfunction of copper homeostasis is linked to severe neurological diseases and cancer. This review provides a compendium of current knowledge regarding the mechanism of copper transfer from the blood system to the Golgi apparatus; this mechanism involves the copper transporter hCtr1, the metallochaperone Atox1, and the ATPases ATP7A/B. We discuss key insights regarding the structural and functional properties of the hCtr1-Atox1-ATP7B cycle, obtained from diverse studies relying on distinct yet complementary biophysical, biochemical, and computational methods. We further address the mechanistic aspects of the cycle that continue to remain elusive. These knowledge gaps must be filled in order to be able to harness our understanding of copper transfer to develop therapeutic approaches with the capacity to modulate copper metabolism.

中文翻译：

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真核系统中的铜贩运：来自实验和计算工作的最新知识。

铜在基本的细胞功能中起着至关重要的作用，由于铜稳态的功能障碍与严重的神经系统疾病和癌症有关，因此铜在细胞中的浓度必须严格控制。这篇综述提供了有关铜从血液系统转移到高尔基体的最新知识的汇编。此机制涉及铜转运蛋白hCtr1，金属伴侣蛋白Atox1和ATPases ATP7A / B。我们讨论了有关hCtr1-Atox1-ATP7B循环的结构和功能特性的关键见解，这些见解是通过依赖独特但互补的生物物理，生化和计算方法的各种研究获得的。我们进一步解决了循环的机械方面，这些方面仍然难以捉摸。