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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| Format: | Article |
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MDPI AG
2020-06-01
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| Series: | Life |
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| Online Access: | https://www.mdpi.com/2075-1729/10/6/98 |
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| author | Carlos Navarro-Paya Maximo Sanz-Hernandez Alfonso De Simone |
| author_facet | Carlos Navarro-Paya Maximo Sanz-Hernandez Alfonso De Simone |
| author_sort | Carlos Navarro-Paya |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T18:51:56Z |
| format | Article |
| id | doaj.art-fd95ad6a69cc44ed8fa6dee5596a7863 |
| institution | Directory Open Access Journal |
| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-10T18:51:56Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Life |
| spelling | doaj.art-fd95ad6a69cc44ed8fa6dee5596a78632023-11-20T05:05:22ZengMDPI AGLife2075-17292020-06-011069810.3390/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 |
| 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 |
| 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 | α-Synuclein membrane binding disorder-to-order transition coarse-grained simulations Parkinson’s disease |
| url | https://www.mdpi.com/2075-1729/10/6/98 |
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