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Direct Observation of the Three Regions in α-Synuclein that Determine its Membrane-Bound Behaviour
α-synuclein (αS) is a protein involved in neurotransmitter release in presynaptic terminals, and whose aberrant aggregation is associated with Parkinson’s disease. In dopaminergic neurons, αS exists in a tightly regulated equilibrium between water-soluble and membrane-associated forms. Here we used...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2014
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4046108/ https://www.ncbi.nlm.nih.gov/pubmed/24871041 http://dx.doi.org/10.1038/ncomms4827 |
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author | Fusco, Giuliana De Simone, Alfonso Tata, Gopinath Vostrikov, Vitaly Vendruscolo, Michele Dobson, Christopher M. Veglia, Gianluigi |
author_facet | Fusco, Giuliana De Simone, Alfonso Tata, Gopinath Vostrikov, Vitaly Vendruscolo, Michele Dobson, Christopher M. Veglia, Gianluigi |
author_sort | Fusco, Giuliana |
collection | PubMed |
description | α-synuclein (αS) is a protein involved in neurotransmitter release in presynaptic terminals, and whose aberrant aggregation is associated with Parkinson’s disease. In dopaminergic neurons, αS exists in a tightly regulated equilibrium between water-soluble and membrane-associated forms. Here we used a combination of solid-state and solution-state NMR spectroscopy to characterize the conformations of αS bound to lipid membranes mimicking the composition and physical properties of synaptic vesicles. The study evidences three αS regions possessing distinct structural and dynamical properties, including an N-terminal helical segment having a role of membrane-anchor, an unstructured C-terminal region that is weakly associated with the membrane, and a central region acting as a sensor of the lipid properties and determining the affinity of αS membrane binding. Taken together, our data define the nature of the interactions of αS with biological membranes and provide insights into their roles in the function and in the molecular processes leading the aggregation of this protein. |
format | Online Article Text |
id | pubmed-4046108 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
record_format | MEDLINE/PubMed |
spelling | pubmed-40461082014-11-29 Direct Observation of the Three Regions in α-Synuclein that Determine its Membrane-Bound Behaviour Fusco, Giuliana De Simone, Alfonso Tata, Gopinath Vostrikov, Vitaly Vendruscolo, Michele Dobson, Christopher M. Veglia, Gianluigi Nat Commun Article α-synuclein (αS) is a protein involved in neurotransmitter release in presynaptic terminals, and whose aberrant aggregation is associated with Parkinson’s disease. In dopaminergic neurons, αS exists in a tightly regulated equilibrium between water-soluble and membrane-associated forms. Here we used a combination of solid-state and solution-state NMR spectroscopy to characterize the conformations of αS bound to lipid membranes mimicking the composition and physical properties of synaptic vesicles. The study evidences three αS regions possessing distinct structural and dynamical properties, including an N-terminal helical segment having a role of membrane-anchor, an unstructured C-terminal region that is weakly associated with the membrane, and a central region acting as a sensor of the lipid properties and determining the affinity of αS membrane binding. Taken together, our data define the nature of the interactions of αS with biological membranes and provide insights into their roles in the function and in the molecular processes leading the aggregation of this protein. 2014-05-29 /pmc/articles/PMC4046108/ /pubmed/24871041 http://dx.doi.org/10.1038/ncomms4827 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Fusco, Giuliana De Simone, Alfonso Tata, Gopinath Vostrikov, Vitaly Vendruscolo, Michele Dobson, Christopher M. Veglia, Gianluigi Direct Observation of the Three Regions in α-Synuclein that Determine its Membrane-Bound Behaviour |
title | Direct Observation of the Three Regions in α-Synuclein that Determine its Membrane-Bound Behaviour |
title_full | Direct Observation of the Three Regions in α-Synuclein that Determine its Membrane-Bound Behaviour |
title_fullStr | Direct Observation of the Three Regions in α-Synuclein that Determine its Membrane-Bound Behaviour |
title_full_unstemmed | Direct Observation of the Three Regions in α-Synuclein that Determine its Membrane-Bound Behaviour |
title_short | Direct Observation of the Three Regions in α-Synuclein that Determine its Membrane-Bound Behaviour |
title_sort | direct observation of the three regions in α-synuclein that determine its membrane-bound behaviour |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4046108/ https://www.ncbi.nlm.nih.gov/pubmed/24871041 http://dx.doi.org/10.1038/ncomms4827 |
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