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- Title
Copper binding to the Alzheimer's disease amyloid precursor protein.
- Authors
Kong, Geoffrey K-W; Miles, Luke A; Crespi, Gabriela A N; Morton, Craig J; Ng, Hooi Ling; Barnham, Kevin J; McKinstry, William J; Cappai, Roberto; Parker, Michael W
- Abstract
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 A beta 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 A beta 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 A beta production. We thus predict that disruption of APP dimers may be a novel therapeutic approach to treat Alzheimer's disease.
- Publication
European biophysics journal : EBJ, 2008, Vol 37, Issue 3, p269
- ISSN
0175-7571
- Publication type
Journal Article
- DOI
10.1007/s00249-007-0234-3