The βA4 amyloid precursor protein binding to copper

FEBS Letters

Hesse, Lars²  Multhaup, Gerd²  Beher, Dirk²  Masters, Colin L.¹ 

[1] Department of Pathology, University of Melbourne, Parkville, Vic. 3052, Australia;Center for Molecular Biology Heidelberg, University Heidelberg, Im Neuenheimer Feld 282, D-69120 Heidelberg, Germany

关键词: Alzheimer's disease;    Copper binding site;    Cell-adhesion;    βA4 amyloid;   

DOI  :  10.1016/0014-5793(94)00658-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Previously it has been shown that the extracellular domain of transmembrane βA4 amyloid precursor protein (APP) includes binding sites for zine(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.

【 授权许可】

Unknown