ATP7A and ATP7B are structurally similar but functionally distinct active copper transporters that regulate copper levels in the human cells and deliver copper to the biosynthetic pathways. Both proteins have a chain of six cytosolic metal-binding domains (MBDs) believed to be involved in the copper-dependent regulation of the activity and intracellular localization of these enzymes. Although all the MBDs are quite similar in structure, their spacing differs markedly between ATP7A and ATP7B. We show by NMR that the long polypeptide between MBD1 and MBD2 of ATP7A forms an additional seventh metastable domain, which we called HMA1A (heavy metal associated domain 1A). The structure of HMA1A resembles the MBDs but contains no copper-binding site. The HMA1A domain, which is unique to ATP7A, may modulate regulatory interactions between MBD1–3, contributing to the distinct functional properties of ATP7A and ATP7B.

ATP7A 和 ATP7B 是结构相似但功能不同的活性铜转运蛋白，可调节人体细胞中的铜水平并将铜输送到生物合成途径。这两种蛋白质都有一个由六个细胞溶质金属结合结构域 (MBD) 组成的链，据信这些结构域与这些酶的活性和细胞内定位的铜依赖性调节有关。尽管所有 MBD 在结构上都非常相似，但它们的间距在 ATP7A 和 ATP7B 之间显着不同。我们通过 NMR 表明，ATP7A 的 MBD1 和 MBD2 之间的长多肽形成了额外的第七个亚稳态结构域，我们称之为 HMA1A（重金属相关结构域 1A）。HMA1A 的结构类似于 MBD，但不含铜结合位点。HMA1A 结构域是 ATP7A 独有的，可以调节 MBD1-3 之间的调节相互作用，