Department of Physiology, Johns Hopkins University, Baltimore, MD 21205, USA.
J Biol Inorg Chem. 2010 Jan;15(1):47-59. doi: 10.1007/s00775-009-0595-4. Epub 2009 Oct 23.
Copper-transporting ATPases (Cu-ATPases) ATP7A and ATP7B play an essential role in human physiological function. Their primary function is to deliver copper to the secretory pathway and export excess copper from the cell for removal or further utilization. Cells employ Cu-ATPases in numerous physiological processes that include the biosynthesis of copper-dependent enzymes, lactation, and response to hypoxia. Biochemical studies of human Cu-ATPases and their orthologs have demonstrated that Cu-ATPases share many common structural and mechanistic characteristics with other members of the P-type ATPase family. Nevertheless, the Cu-ATPases have a unique coordinate environment for their ligands, copper and ATP, and additional domains that are required for sophisticated regulation of their intracellular localization and activity. Here, we review recent progress that has been made in understanding the structure of Cu-ATPases from the analysis of their individual domains and orthologs from microorganisms, and speculate about the implications of these findings for the function and regulation of human copper pumps.
铜转运 ATP 酶（Cu-ATPases）ATP7A 和 ATP7B 在人体生理功能中发挥着重要作用。它们的主要功能是将铜输送到分泌途径，并将多余的铜从细胞内排出或进一步利用。细胞在许多生理过程中都利用 Cu-ATPases，包括铜依赖性酶的生物合成、泌乳和对缺氧的反应。对人类 Cu-ATPases 及其同源物的生化研究表明，Cu-ATPases 与 P 型 ATP 酶家族的其他成员具有许多共同的结构和机制特征。然而，Cu-ATPases 具有独特的配体（铜和 ATP）协调环境，以及用于其细胞内定位和活性的复杂调节的额外结构域。在这里，我们综述了近年来在理解 Cu-ATPases 结构方面的进展，包括对其各个结构域的分析，以及对微生物同源物的分析，并推测了这些发现对人类铜泵功能和调节的意义。
