1owt: Difference between revisions
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==Overview== | ==Overview== | ||
A major source of free radical production in the brain derives from | 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. | ||
==Disease== | ==Disease== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Barnham, K | [[Category: Barnham, K J.]] | ||
[[Category: Beyreuther, K.]] | [[Category: Beyreuther, K.]] | ||
[[Category: Cappai, R.]] | [[Category: Cappai, R.]] | ||
[[Category: Curtain, C | [[Category: Curtain, C C.]] | ||
[[Category: Galatis, D.]] | [[Category: Galatis, D.]] | ||
[[Category: Hinds, M | [[Category: Hinds, M G.]] | ||
[[Category: Masters, C | [[Category: Masters, C L.]] | ||
[[Category: McKinstry, W | [[Category: McKinstry, W J.]] | ||
[[Category: Morton, C | [[Category: Morton, C J.]] | ||
[[Category: Multhaup, G.]] | [[Category: Multhaup, G.]] | ||
[[Category: Norton, R | [[Category: Norton, R S.]] | ||
[[Category: Parker, M | [[Category: Parker, M W.]] | ||
[[Category: White, A | [[Category: White, A R.]] | ||
[[Category: Williamson, N | [[Category: Williamson, N A.]] | ||
[[Category: beta-alpha-beta-beta]] | [[Category: beta-alpha-beta-beta]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:22:37 2008'' | ||
Revision as of 15:22, 21 February 2008
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Structure of the Alzheimer's disease amyloid precursor protein copper binding domain
OverviewOverview
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.
DiseaseDisease
Known diseases associated with this structure: Alzheimer disease-1, APP-related OMIM:[104760], Amyloidosis, cerebroarterial, Dutch type OMIM:[104760], Amyloidosis, cerebroarterial, Iowa type OMIM:[104760], Blood group, P system OMIM:[607922]
About this StructureAbout this Structure
1OWT is a Single protein structure of sequence from Homo sapiens. The following page contains interesting information on the relation of 1OWT with [Amyloid-beta Precursor Protein]. Full crystallographic information is available from OCA.
ReferenceReference
Structure of the Alzheimer's disease amyloid precursor protein copper binding domain. A regulator of neuronal copper homeostasis., Barnham KJ, McKinstry WJ, Multhaup G, Galatis D, Morton CJ, Curtain CC, Williamson NA, White AR, Hinds MG, Norton RS, Beyreuther K, Masters CL, Parker MW, Cappai R, J Biol Chem. 2003 May 9;278(19):17401-7. Epub 2003 Feb 28. PMID:12611883
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