Voskoboinik I, Greenough M, La Fontaine S, Mercer J F, Camakaris J
Department of Genetics, University of Melbourne, Parkville, Victoria, 3010, Australia.
Biochem Biophys Res Commun. 2001 Mar 9;281(4):966-70. doi: 10.1006/bbrc.2001.4445.
The Wilson protein (WND; ATP7B) is an essential component of copper homeostasis. Mutations in the ATP7B gene result in Wilson disease, which is characterised by hepatotoxicity and neurological disturbances. In this paper, we provide the first direct biochemical evidence that the WND protein functions as a copper-translocating P-type ATPase in mammalian cells. Importantly, we have shown that the mutation of the conserved Met1386 to Val, in the Atp7B for the mouse model of Wilson disease, toxic milk (tx), caused a loss of Cu-translocating activity. These investigations provide strong evidence that the toxic milk mouse is a valid model for Wilson disease and demonstrate a link between the loss of catalytic function of WND and the Wilson disease phenotype.
威尔逊蛋白（WND；ATP7B）是铜稳态的重要组成部分。ATP7B基因突变会导致威尔逊病，其特征为肝毒性和神经功能障碍。在本文中，我们首次提供了直接的生化证据，证明WND蛋白在哺乳动物细胞中作为一种铜转运P型ATP酶发挥作用。重要的是，我们已经表明，在威尔逊病小鼠模型——毒奶（tx）的Atp7B中，保守的甲硫氨酸1386突变为缬氨酸会导致铜转运活性丧失。这些研究提供了强有力的证据，证明毒奶小鼠是威尔逊病的有效模型，并证明了WND催化功能丧失与威尔逊病表型之间的联系。
