1OWT
Structure of the Alzheimer's disease amyloid precursor protein copper binding domain
Summary for 1OWT
| Entry DOI | 10.2210/pdb1owt/pdb |
| Descriptor | Amyloid beta A4 protein (1 entity in total) |
| Functional Keywords | beta-alpha-beta-beta, apoptosis |
| Biological source | Homo sapiens (human) |
| Cellular location | Membrane; Single-pass type I membrane protein: P05067 |
| Total number of polymer chains | 1 |
| Total formula weight | 7588.81 |
| Authors | Barnham, K.J.,McKinstry, W.J.,Multhaup, G.,Galatis, D.,Morton, C.J.,Curtain, C.C.,Williamson, N.A.,White, A.R.,Hinds, M.G.,Norton, R.S.,Beyreuther, K.,Masters, C.L.,Parker, M.W.,Cappai, R. (deposition date: 2003-03-30, release date: 2003-05-13, Last modification date: 2024-10-30) |
| Primary citation | Barnham, K.J.,McKinstry, W.J.,Multhaup, G.,Galatis, D.,Morton, C.J.,Curtain, C.C.,Williamson, N.A.,White, A.R.,Hinds, M.G.,Norton, R.S.,Beyreuther, K.,Masters, C.L.,Parker, M.W.,Cappai, R. Structure of the Alzheimer's Disease Amyloid Precursor Protein Copper Binding Domain. A REGULATOR OF NEURONAL COPPER HOMEOSTASIS. J.Biol.Chem., 278:17401-17407, 2003 Cited by PubMed Abstract: A major source of free radical production in the brain derives from copper. To prevent metal-mediated oxidative stress, cells have evolved complex metal transport systems. The Alzheimer's disease amyloid precursor protein (APP) is a major regulator of neuronal copper homeostasis. APP knockout mice have elevated copper levels in the cerebral cortex, whereas APP-overexpressing transgenic mice have reduced brain copper levels. Importantly, copper binding to APP can greatly reduce amyloid beta production in vitro. To understand this interaction at the molecular level we solved the structure of the APP copper binding domain (CuBD) and found that it contains a novel copper binding site that favors Cu(I) coordination. The surface location of this site, structural homology of CuBD to copper chaperones, and the role of APP in neuronal copper homeostasis are consistent with the CuBD acting as a neuronal metallotransporter. PubMed: 12611883DOI: 10.1074/jbc.M300629200 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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