The Neuronal Adaptor Protein X11α Interacts with the Copper Chaperone for SOD1 and Regulates SOD1 Activity*-猫眼课题宝

神经元适配器蛋白 X11α 与 SOD1 的铜伴侣相互作用并调节 SOD1 活性*

DOI：

发表时间：

2001

期刊：

Journal of Biological Chemistry

影响因子：

4.8

通讯作者：

中科院分区：

生物学2区

文献类型：

作者：

D. McLoughlin;C. Standen;K. Lau;S. Ackerley;Thomas P. Bartnikas;J. Gitlin;Christopher C. J. Miller

神经元接头蛋白X11α参与多蛋白复合物的形成和细胞内运输。它包含一系列离散的蛋白质-蛋白质相互作用结构域，包括两个连续的c端PDZ结构域。我们利用酵母双杂交系统筛选与人X11α PDZ结构域相互作用的蛋白，并分离出Cu， zn -超氧化物歧化酶-1 （CCS）铜伴侣蛋白II和III结构域的克隆。X11α/CCS相互作用在共免疫沉淀研究和谷胱甘肽-转移酶融合蛋白下拉实验中得到证实，并通过X11α的PDZ2和CCS结构域III羧基末端的一个序列介导。CCS将铜辅助因子传递给抗氧化剂超氧化物歧化酶-1 （SOD1）酶，并且是其活性所必需的。过表达X11α可抑制SOD1活性，表明X11α与CCS结合可抑制SOD1活性。X11α还与另一种在神经元中发现的铜结合蛋白相互作用，即阿尔茨海默病淀粉样蛋白前体蛋白。因此，X11α可能参与神经元内铜的稳态。

The neuronal adaptor protein X11α participates in the formation of multiprotein complexes and intracellular trafficking. It contains a series of discrete protein-protein interaction domains including two contiguous C-terminal PDZ domains. We used the yeast two-hybrid system to screen for proteins that interact with the PDZ domains of human X11α, and we isolated a clone encoding domains II and III of the copper chaperone for Cu,Zn-superoxide dismutase-1 (CCS). The X11α/CCS interaction was confirmed in coimmunoprecipitation studies plus glutathioneS-transferase fusion protein pull-down assays and was shown to be mediated via PDZ2 of X11α and a sequence within the carboxyl terminus of domain III of CCS. CCS delivers the copper cofactor to the antioxidant superoxide dismutase-1 (SOD1) enzyme and is required for its activity. Overexpression of X11α inhibited SOD1 activity in transfected Chinese hamster ovary cells which suggests that X11α binding to CCS is inhibitory to SOD1 activation. X11α also interacts with another copper-binding protein found in neurons, the Alzheimer's disease amyloid precursor protein. Thus, X11α may participate in copper homeostasis within neurons.