Copper binding to the Alzheimer’s disease amyloid precursor protein
| العنوان: | Copper binding to the Alzheimer’s disease amyloid precursor protein |
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| المؤلفون: | Michael W. Parker, Roberto Cappai, William J. McKinstry, Craig J. Morton, Gabriela A. N. Crespi, Luke A. Miles, Hooi Ling Ng, Kevin J. Barnham, Geoffrey Kwai-Wai Kong |
| المصدر: | European Biophysics Journal |
| بيانات النشر: | Springer Science and Business Media LLC, 2007. |
| سنة النشر: | 2007 |
| مصطلحات موضوعية: | Protein Conformation, Proteolysis, Molecular Sequence Data, Receptor signalling, Biophysics, Down-Regulation, Review, Plasma protein binding, Models, Biological, Amyloid beta-Protein Precursor, chemistry.chemical_compound, Protein structure, Alzheimer Disease, Amyloid precursor protein, medicine, Metalloprotein, Animals, Humans, Binding site, chemistry.chemical_classification, Amyloid beta-Peptides, Binding Sites, biology, medicine.diagnostic_test, Spectrum Analysis, General Medicine, medicine.disease, Beta-peptide, Biochemistry, chemistry, Crystal structures, biology.protein, Alzheimer's disease, Dimerization, Protein Processing, Post-Translational, Alzheimer’s disease, Copper, Copper binding, Protein Binding |
| الوصف: | 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. |
| تدمد: | 1432-1017 0175-7571 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ab6fdabc368e9ec3863608107a18a857Test https://doi.org/10.1007/s00249-007-0234-3Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ab6fdabc368e9ec3863608107a18a857 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14321017 01757571 |
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