Copper binding to the Alzheimer’s disease amyloid precursor protein

被引：0
作者：
Geoffrey K.-W. Kong
Luke A. Miles
Gabriela A. N. Crespi
Craig J. Morton
Hooi Ling Ng
Kevin J. Barnham
William J. McKinstry
Roberto Cappai
Michael W. Parker
机构：
[1] St. Vincent’s Institute of Medical Research,Biota Structural Biology Laboratory
[2] The University of Melbourne,Department of Pathology
[3] Institute of Victoria,The Mental Health Research
[4] The University of Melbourne,Bio21 Molecular Science and Biotechnology Institute
[5] The University of Melbourne,Centre for Neuroscience
[6] Max-Planck-Institut für Biochemie,Abt. Molekulare Strukturbiologie
[7] Pfizer Animal Health,undefined
来源：
European Biophysics Journal | 2008年 / 37卷
关键词：
Alzheimer’s disease; Amyloid precursor protein; Copper binding; Crystal structures; Receptor signalling;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
Alzheimer’s disease is the fourth biggest killer in developed countries. Amyloid precursor protein (APP) plays a central role in the development of the disease, through the generation of a peptide called Aβ by proteolysis of the precursor protein. APP can function as a metalloprotein and modulate copper transport via its extracellular copper binding domain (CuBD). Copper binding to this domain has been shown to reduce Aβ levels and hence a molecular understanding of the interaction between metal and protein could lead to the development of novel therapeutics to treat the disease. We have recently determined the three-dimensional structures of apo and copper bound forms of CuBD. The structures provide a mechanism by which CuBD could readily transfer copper ions to other proteins. Importantly, the lack of significant conformational changes to CuBD on copper binding suggests a model in which copper binding affects the dimerisation state of APP leading to reduction in Aβ production. We thus predict that disruption of APP dimers may be a novel therapeutic approach to treat Alzheimer’s disease.
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页码：269 / 279
页数：10
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