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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Main Authors:	Carlos Navarro-Paya, Maximo Sanz-Hernandez, Alfonso De Simone
Format:	Article
Language:	English
Published:	MDPI AG 2020-06-01
Series:	Life
Subjects:	α-Synuclein membrane binding disorder-to-order transition coarse-grained simulations Parkinson’s disease
Online Access:	https://www.mdpi.com/2075-1729/10/6/98

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spelling	doaj-fd95ad6a69cc44ed8fa6dee5596a78632020-11-25T03:05:24ZengMDPI AGLife2075-17292020-06-0110989810.3390/life10060098In Silico Study of the Mechanism of Binding of the N-Terminal Region of α Synuclein to Synaptic-Like MembranesCarlos Navarro-Paya0Maximo Sanz-Hernandez1Alfonso De Simone2Department of Life Sciences, Imperial College London, South Kensington, London SW7 2AX, UKDepartment of Life Sciences, Imperial College London, South Kensington, London SW7 2AX, UKDepartment of Life Sciences, Imperial College London, South Kensington, London SW7 2AX, UKThe 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.https://www.mdpi.com/2075-1729/10/6/98α-Synucleinmembrane bindingdisorder-to-order transitioncoarse-grained simulationsParkinson’s disease
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Carlos Navarro-Paya Maximo Sanz-Hernandez Alfonso De Simone
spellingShingle	Carlos Navarro-Paya Maximo Sanz-Hernandez Alfonso De Simone In Silico Study of the Mechanism of Binding of the N-Terminal Region of α Synuclein to Synaptic-Like Membranes Life α-Synuclein membrane binding disorder-to-order transition coarse-grained simulations Parkinson’s disease
author_facet	Carlos Navarro-Paya Maximo Sanz-Hernandez Alfonso De Simone
author_sort	Carlos Navarro-Paya
title	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_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_sort	in silico study of the mechanism of binding of the n-terminal region of α synuclein to synaptic-like membranes
publisher	MDPI AG
series	Life
issn	2075-1729
publishDate	2020-06-01
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.
topic	α-Synuclein membrane binding disorder-to-order transition coarse-grained simulations Parkinson’s disease
url	https://www.mdpi.com/2075-1729/10/6/98
work_keys_str_mv	AT carlosnavarropaya insilicostudyofthemechanismofbindingofthenterminalregionofasynucleintosynapticlikemembranes AT maximosanzhernandez insilicostudyofthemechanismofbindingofthenterminalregionofasynucleintosynapticlikemembranes AT alfonsodesimone insilicostudyofthemechanismofbindingofthenterminalregionofasynucleintosynapticlikemembranes
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In Silico Study of the Mechanism of Binding of the N-Terminal Region of α Synuclein to Synaptic-Like Membranes

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