Copper(II) and the pathological H50Q α-synuclein mutant: Environment meets genetics
Copper is one of the metals described to bind the Parkinson disease-related protein α-synuclein (aSyn), and to promote its aggregation. Although histidine at position 50 in the aSyn sequence is one of the most studied copper-anchoring sites, its precise role in copper binding and aSyn aggregation is...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2017-01-01
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| Series: | Communicative & Integrative Biology |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/19420889.2016.1270484 |
| _version_ | 1818919105698201600 |
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| author | Anna Villar-Piqué Giulia Rossetti Salvador Ventura Paolo Carloni Claudio O. Fernández Tiago Fleming Outeiro |
| author_facet | Anna Villar-Piqué Giulia Rossetti Salvador Ventura Paolo Carloni Claudio O. Fernández Tiago Fleming Outeiro |
| author_sort | Anna Villar-Piqué |
| collection | DOAJ |
| description | Copper is one of the metals described to bind the Parkinson disease-related protein α-synuclein (aSyn), and to promote its aggregation. Although histidine at position 50 in the aSyn sequence is one of the most studied copper-anchoring sites, its precise role in copper binding and aSyn aggregation is still unclear. Previous studies suggested that this residue does not significantly affect copper-mediated aSyn aggregation. However, our findings showed that the aggregation of the pathological H50Q aSyn mutant is enhanced by copper hints otherwise. Despite the inexistence of a model for aSyn H50Q-copper complexation, we discuss possible mechanisms by which this metal contributes to the misfolding and self-assembly of this particular aSyn mutant. Considering the genetic association of the H50Q mutation with familial forms of Parkinson disease, and the fact that copper homeostasis is deregulated in this disorder, understanding the interplay between both factors will shed light into the molecular and cellular mechanisms triggering the development and spreading of the aSyn pathology. |
| first_indexed | 2024-12-20T01:00:34Z |
| format | Article |
| id | doaj.art-6aff8d7663a6492dad392f2582205b6d |
| institution | Directory Open Access Journal |
| issn | 1942-0889 |
| language | English |
| last_indexed | 2024-12-20T01:00:34Z |
| publishDate | 2017-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Communicative & Integrative Biology |
| spelling | doaj.art-6aff8d7663a6492dad392f2582205b6d2022-12-21T19:58:59ZengTaylor & Francis GroupCommunicative & Integrative Biology1942-08892017-01-0110110.1080/19420889.2016.12704841270484Copper(II) and the pathological H50Q α-synuclein mutant: Environment meets geneticsAnna Villar-Piqué0Giulia Rossetti1Salvador Ventura2Paolo Carloni3Claudio O. Fernández4Tiago Fleming Outeiro5University Medical Centre GöttingenComputational Biomedicine, Institute for Advanced Simulation IAS-5 and Institute of Neuroscience and Medicine INM-9Institut de Biotecnologia i Biomedicina and Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de BarcelonaComputational Biomedicine, Institute for Advanced Simulation IAS-5 and Institute of Neuroscience and Medicine INM-9Max Planck Laboratory for Structural Biology, Chemistry, and Molecular Biophysics of Rosario, Universidad Nacional de RosarioUniversity Medical Centre GöttingenCopper is one of the metals described to bind the Parkinson disease-related protein α-synuclein (aSyn), and to promote its aggregation. Although histidine at position 50 in the aSyn sequence is one of the most studied copper-anchoring sites, its precise role in copper binding and aSyn aggregation is still unclear. Previous studies suggested that this residue does not significantly affect copper-mediated aSyn aggregation. However, our findings showed that the aggregation of the pathological H50Q aSyn mutant is enhanced by copper hints otherwise. Despite the inexistence of a model for aSyn H50Q-copper complexation, we discuss possible mechanisms by which this metal contributes to the misfolding and self-assembly of this particular aSyn mutant. Considering the genetic association of the H50Q mutation with familial forms of Parkinson disease, and the fact that copper homeostasis is deregulated in this disorder, understanding the interplay between both factors will shed light into the molecular and cellular mechanisms triggering the development and spreading of the aSyn pathology.http://dx.doi.org/10.1080/19420889.2016.1270484α-synucleinamyloidcopperH50Q mutationParkinson diseaseprotein aggregation |
| spellingShingle | Anna Villar-Piqué Giulia Rossetti Salvador Ventura Paolo Carloni Claudio O. Fernández Tiago Fleming Outeiro Copper(II) and the pathological H50Q α-synuclein mutant: Environment meets genetics Communicative & Integrative Biology α-synuclein amyloid copper H50Q mutation Parkinson disease protein aggregation |
| title | Copper(II) and the pathological H50Q α-synuclein mutant: Environment meets genetics |
| title_full | Copper(II) and the pathological H50Q α-synuclein mutant: Environment meets genetics |
| title_fullStr | Copper(II) and the pathological H50Q α-synuclein mutant: Environment meets genetics |
| title_full_unstemmed | Copper(II) and the pathological H50Q α-synuclein mutant: Environment meets genetics |
| title_short | Copper(II) and the pathological H50Q α-synuclein mutant: Environment meets genetics |
| title_sort | copper ii and the pathological h50q α synuclein mutant environment meets genetics |
| topic | α-synuclein amyloid copper H50Q mutation Parkinson disease protein aggregation |
| url | http://dx.doi.org/10.1080/19420889.2016.1270484 |
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