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Binding of Dopamine to Alpha-Synuclein is Mediated by Specific Conformational States
Parkinson’s disease is the second most common neurodegenerative disorder, in which both alpha-synuclein (α-syn) and dopamine (DA) have a critical role. α-Syn is known to be natively unstructured in equilibrium with subpopulations of more compact structures. It is these compact structures that are th...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer US
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3738842/ https://www.ncbi.nlm.nih.gov/pubmed/23817832 http://dx.doi.org/10.1007/s13361-013-0676-z |
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author | Illes-Toth, Eva Dalton, Caroline F. Smith, David P. |
author_facet | Illes-Toth, Eva Dalton, Caroline F. Smith, David P. |
author_sort | Illes-Toth, Eva |
collection | PubMed |
description | Parkinson’s disease is the second most common neurodegenerative disorder, in which both alpha-synuclein (α-syn) and dopamine (DA) have a critical role. α-Syn is known to be natively unstructured in equilibrium with subpopulations of more compact structures. It is these compact structures that are thought to be linked to amyloid formation. In the presence of DA, α-syn yields a diverse range of SDS-resistant, non-amyloid oligomers, however the precursor state conformation has not been established. Here, three DA molecules have been observed to bind per α-syn monomer by electrospray-ionization-ion mobility spectrometry-mass spectrometry (ESI-IMS-MS). Each of these DA molecules binds exclusively to the extended conformation of α-syn, and binding is not observed in the compact state of the protein. Measurements of collisional cross sectional areas show that the incremental uptake of DA pushes the protein towards a highly extended population, becoming fully populated upon the binding of three DA ligands. Tyrosine (Tyr) as a closely related structural analog, exhibited limited binding to the protein as compared with DA, with a maximum of two ligands being observed. Those Tyr ligands that do bind were observed as adducts to the extended conformation akin to DA. These findings suggest DA is able to modulate α-syn self-assembly by inducing the population of a highly extended state. [Figure: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13361-013-0676-z) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-3738842 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-37388422013-08-13 Binding of Dopamine to Alpha-Synuclein is Mediated by Specific Conformational States Illes-Toth, Eva Dalton, Caroline F. Smith, David P. J Am Soc Mass Spectrom Research Article Parkinson’s disease is the second most common neurodegenerative disorder, in which both alpha-synuclein (α-syn) and dopamine (DA) have a critical role. α-Syn is known to be natively unstructured in equilibrium with subpopulations of more compact structures. It is these compact structures that are thought to be linked to amyloid formation. In the presence of DA, α-syn yields a diverse range of SDS-resistant, non-amyloid oligomers, however the precursor state conformation has not been established. Here, three DA molecules have been observed to bind per α-syn monomer by electrospray-ionization-ion mobility spectrometry-mass spectrometry (ESI-IMS-MS). Each of these DA molecules binds exclusively to the extended conformation of α-syn, and binding is not observed in the compact state of the protein. Measurements of collisional cross sectional areas show that the incremental uptake of DA pushes the protein towards a highly extended population, becoming fully populated upon the binding of three DA ligands. Tyrosine (Tyr) as a closely related structural analog, exhibited limited binding to the protein as compared with DA, with a maximum of two ligands being observed. Those Tyr ligands that do bind were observed as adducts to the extended conformation akin to DA. These findings suggest DA is able to modulate α-syn self-assembly by inducing the population of a highly extended state. [Figure: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13361-013-0676-z) contains supplementary material, which is available to authorized users. Springer US 2013-07-02 2013 /pmc/articles/PMC3738842/ /pubmed/23817832 http://dx.doi.org/10.1007/s13361-013-0676-z Text en © The Author(s) 2013 https://creativecommons.org/licenses/by/2.0/ Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. |
spellingShingle | Research Article Illes-Toth, Eva Dalton, Caroline F. Smith, David P. Binding of Dopamine to Alpha-Synuclein is Mediated by Specific Conformational States |
title | Binding of Dopamine to Alpha-Synuclein is Mediated by Specific Conformational States |
title_full | Binding of Dopamine to Alpha-Synuclein is Mediated by Specific Conformational States |
title_fullStr | Binding of Dopamine to Alpha-Synuclein is Mediated by Specific Conformational States |
title_full_unstemmed | Binding of Dopamine to Alpha-Synuclein is Mediated by Specific Conformational States |
title_short | Binding of Dopamine to Alpha-Synuclein is Mediated by Specific Conformational States |
title_sort | binding of dopamine to alpha-synuclein is mediated by specific conformational states |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3738842/ https://www.ncbi.nlm.nih.gov/pubmed/23817832 http://dx.doi.org/10.1007/s13361-013-0676-z |
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