Hesse L, Beher D, Masters C L, Multhaup G
Center for Molecular Biology Heidelberg, University Heidelberg, Germany.
FEBS Lett. 1994 Jul 25;349(1):109-16. doi: 10.1016/0014-5793(94)00658-x.
Previously it has been shown that the extracellular domain of transmembrane beta A4 amyloid precursor protein (APP) includes binding sites for zinc(II) and for molecules of the extracellular matrix such as collagen, laminin and the heparin sulfate chains of proteoglycans (HSPGs). Here we report that APP also binds copper ions. A copper type II binding site was located within residues 135-155 of the cysteine-rich domain of APP695 which is present in all eight APP splice isoforms known so far. The two essential histidines in the type II copper binding site of APP are conserved in the related protein APLP2. Copper(II) binding is shown to inhibit homophilic APP binding. The identification of a copper(II) binding site in APP suggests that APP and APLP2 may be involved in electron transfer and radical reactions.
此前已有研究表明，跨膜β淀粉样前体蛋白（APP）的细胞外结构域包含锌（II）结合位点以及细胞外基质分子（如胶原蛋白、层粘连蛋白和蛋白聚糖的硫酸乙酰肝素链）的结合位点。在此我们报告APP也能结合铜离子。在APP695富含半胱氨酸结构域的135 - 155位残基内发现了一个II型铜结合位点，该位点存在于目前已知的所有八种APP剪接异构体中。APP的II型铜结合位点中的两个必需组氨酸在相关蛋白APLP2中保守。已表明铜（II）结合可抑制APP的同源结合。APP中II型铜结合位点的鉴定表明，APP和APLP2可能参与电子转移和自由基反应。
