Academic Journal
Copper(I)-α-Synuclein Interaction: Structural Description of Two Independent and Competing Metal Binding Sites.
| العنوان: | Copper(I)-α-Synuclein Interaction: Structural Description of Two Independent and Competing Metal Binding Sites. |
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| المؤلفون: | Camponeschi F, Valensin D, Dell'acqua S, Casella L, Monzani E, Gaggelli E, Valensin G., TESSARI, ISABELLA, BUBACCO, LUIGI |
| المساهمون: | Camponeschi, F, Valensin, D, Tessari, Isabella, Bubacco, Luigi, Dell'Acqua, S, Casella, L, Monzani, E, Gaggelli, E, Valensin, G. |
| بيانات النشر: | AMER CHEMICAL SOC, 1155 16TH ST, NW, WASHINGTON, DC 20036 USA |
| سنة النشر: | 2013 |
| المجموعة: | Padua Research Archive (IRIS - Università degli Studi di Padova) |
| مصطلحات موضوعية: | alpha synuclein, nuclear magnetic resonance spectroscopy, Copper, circular dichroism |
| الوصف: | The aggregation of alpha-synuclein (alpha S) is a critical step in the etiology of Parkinson's disease. Metal ions such as copper and iron have been shown to bind alpha S, enhancing its fibrillation rate in vitro, alpha S is also susceptible to copper-catalyzed oxidation that involves the reduction of Cu-II to Cu-I and the conversion of O-2 into reactive oxygen species. The mechanism of the reaction is highly selective and site-specific and involves interactions of the protein with both oxidation states of the copper ion. The reaction can induce oxidative modification of the protein, which generally leads to extensive protein oligomerization and precipitation. Cu-II binding to alpha S has been extensively characterized, indicating the N terminus and His-50 as binding donor residues. In this study, we have investigated alpha S-Cu-I interaction by means of NMR and circular dichroism analysis on the full-length protein (alpha S1-140) and on two, designed ad hoc, model peptides: alpha S1-15 and alpha S113-130. In order to identify and characterize the metal binding environment in full-length aS, in addition to Cu-I, we have also used Ag-I as a probe for Cu-I binding. Two distinct Cu-I/Ag-I binding domains with comparable affinities have been identified. The structural rearrangements induced by the metal ions and the metal coordination spheres of both sites have been extensively characterized. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | STAMPA |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/23343468; info:eu-repo/semantics/altIdentifier/wos/WOS:000314627700025; volume:52; firstpage:1358; lastpage:1367; numberofpages:10; journal:INORGANIC CHEMISTRY; http://hdl.handle.net/11577/2554482; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84873355344 |
| DOI: | 10.1021/ic302050m |
| الاتاحة: | http://hdl.handle.net/11577/2554482 https://doi.org/10.1021/ic302050m |
| رقم الانضمام: | edsbas.93F57867 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1021/ic302050m |
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