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In Silico Study of the Mechanism of Binding of the N-Terminal Region of α Synuclein to Synaptic-Like Membranes

The membrane binding by α-synuclein (αS), a presynaptic protein whose aggregation is strongly linked with Parkinson’s disease, influences its biological behavior under functional and pathological conditions. This interaction requires a conformational transition from a disordered-unbound to a partial...

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Autores principales: Navarro-Paya, Carlos, Sanz-Hernandez, Maximo, De Simone, Alfonso
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344899/
https://www.ncbi.nlm.nih.gov/pubmed/32604928
http://dx.doi.org/10.3390/life10060098
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author Navarro-Paya, Carlos
Sanz-Hernandez, Maximo
De Simone, Alfonso
author_facet Navarro-Paya, Carlos
Sanz-Hernandez, Maximo
De Simone, Alfonso
author_sort Navarro-Paya, Carlos
collection PubMed
description The membrane binding by α-synuclein (αS), a presynaptic protein whose aggregation is strongly linked with Parkinson’s disease, influences its biological behavior under functional and pathological conditions. This interaction requires a conformational transition from a disordered-unbound to a partially helical membrane-bound state of the protein. In the present study, we used enhanced coarse-grained MD simulations to characterize the sequence and conformational determinants of the binding to synaptic-like vesicles by the N-terminal region of αS. This region is the membrane anchor and is of crucial importance for the properties of the physiological monomeric state of αS as well as for its aberrant aggregates. These results identify the key factors that play a role in the binding of αS with synaptic lipid bilayers in both membrane-tethered and membrane-locked conformational states.
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spelling pubmed-73448992020-07-09 In Silico Study of the Mechanism of Binding of the N-Terminal Region of α Synuclein to Synaptic-Like Membranes Navarro-Paya, Carlos Sanz-Hernandez, Maximo De Simone, Alfonso Life (Basel) Article The membrane binding by α-synuclein (αS), a presynaptic protein whose aggregation is strongly linked with Parkinson’s disease, influences its biological behavior under functional and pathological conditions. This interaction requires a conformational transition from a disordered-unbound to a partially helical membrane-bound state of the protein. In the present study, we used enhanced coarse-grained MD simulations to characterize the sequence and conformational determinants of the binding to synaptic-like vesicles by the N-terminal region of αS. This region is the membrane anchor and is of crucial importance for the properties of the physiological monomeric state of αS as well as for its aberrant aggregates. These results identify the key factors that play a role in the binding of αS with synaptic lipid bilayers in both membrane-tethered and membrane-locked conformational states. MDPI 2020-06-26 /pmc/articles/PMC7344899/ /pubmed/32604928 http://dx.doi.org/10.3390/life10060098 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Navarro-Paya, Carlos
Sanz-Hernandez, Maximo
De Simone, Alfonso
In Silico Study of the Mechanism of Binding of the N-Terminal Region of α Synuclein to Synaptic-Like Membranes
title In Silico Study of the Mechanism of Binding of the N-Terminal Region of α Synuclein to Synaptic-Like Membranes
title_full In Silico Study of the Mechanism of Binding of the N-Terminal Region of α Synuclein to Synaptic-Like Membranes
title_fullStr In Silico Study of the Mechanism of Binding of the N-Terminal Region of α Synuclein to Synaptic-Like Membranes
title_full_unstemmed In Silico Study of the Mechanism of Binding of the N-Terminal Region of α Synuclein to Synaptic-Like Membranes
title_short In Silico Study of the Mechanism of Binding of the N-Terminal Region of α Synuclein to Synaptic-Like Membranes
title_sort in silico study of the mechanism of binding of the n-terminal region of α synuclein to synaptic-like membranes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344899/
https://www.ncbi.nlm.nih.gov/pubmed/32604928
http://dx.doi.org/10.3390/life10060098
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