The Synaptotagmin-1 C2B Domain Is a Key Regulator in the Stabilization of the Fusion Pore
- Autores
- Caparotta, Marcelo Rubén; Tomes, Claudia Nora; Mayorga, Luis Segundo; Masone, Diego Fernando
- Año de publicación
- 2020
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Fusion pores serve as an effective mechanism to connect intracellular organelles and release vesicle contents during exocytosis. A complex lipid rearrangement takes place as membranes approximate, bend, fuse, and establish a traversing water channel to define the fusion pore, linking initially isolated chambers. Thermodynamically, the process is unfavorable and thought to be mediated by specialized proteins. In this work, we have developed a reaction coordinate to induce fusion pores from initially flat and parallel lipid bilayers and we have used it to describe the effects of the synaptotagmin-1 C2B domain during the process. We have obtained free-energy profiles of the whole lipid reorganization in biologically realistic membranes, going from planar and parallel bilayers through stalk hemifusion to water channel formation. Our results point to a lysine-rich polybasic region on synaptotagmin-1 C2B as the key to lipid reorganization control through the formation of phosphatidylinositol bisphosphate clusters that stabilize the fusion pore.
Fil: Caparotta, Marcelo Rubén. Universidad Nacional de Cuyo; Argentina
Fil: Tomes, Claudia Nora. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Fil: Mayorga, Luis Segundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Fil: Masone, Diego Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina - Materia
-
synaptotagmin
fusion pore
molecular dynamics
lipids - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/140993
Ver los metadatos del registro completo
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The Synaptotagmin-1 C2B Domain Is a Key Regulator in the Stabilization of the Fusion PoreCaparotta, Marcelo RubénTomes, Claudia NoraMayorga, Luis SegundoMasone, Diego Fernandosynaptotagminfusion poremolecular dynamicslipidshttps://purl.org/becyt/ford/1.2https://purl.org/becyt/ford/1Fusion pores serve as an effective mechanism to connect intracellular organelles and release vesicle contents during exocytosis. A complex lipid rearrangement takes place as membranes approximate, bend, fuse, and establish a traversing water channel to define the fusion pore, linking initially isolated chambers. Thermodynamically, the process is unfavorable and thought to be mediated by specialized proteins. In this work, we have developed a reaction coordinate to induce fusion pores from initially flat and parallel lipid bilayers and we have used it to describe the effects of the synaptotagmin-1 C2B domain during the process. We have obtained free-energy profiles of the whole lipid reorganization in biologically realistic membranes, going from planar and parallel bilayers through stalk hemifusion to water channel formation. Our results point to a lysine-rich polybasic region on synaptotagmin-1 C2B as the key to lipid reorganization control through the formation of phosphatidylinositol bisphosphate clusters that stabilize the fusion pore.Fil: Caparotta, Marcelo Rubén. Universidad Nacional de Cuyo; ArgentinaFil: Tomes, Claudia Nora. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Mayorga, Luis Segundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Masone, Diego Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaAmerican Chemical Society2020-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/140993Caparotta, Marcelo Rubén; Tomes, Claudia Nora; Mayorga, Luis Segundo; Masone, Diego Fernando; The Synaptotagmin-1 C2B Domain Is a Key Regulator in the Stabilization of the Fusion Pore; American Chemical Society; Journal of Chemical Theory and Computation; 16; 12; 11-2020; 7840-78511549-9618CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1021/acs.jctc.0c00734info:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/10.1021/acs.jctc.0c00734info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:46:33Zoai:ri.conicet.gov.ar:11336/140993instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:46:33.575CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
The Synaptotagmin-1 C2B Domain Is a Key Regulator in the Stabilization of the Fusion Pore |
title |
The Synaptotagmin-1 C2B Domain Is a Key Regulator in the Stabilization of the Fusion Pore |
spellingShingle |
The Synaptotagmin-1 C2B Domain Is a Key Regulator in the Stabilization of the Fusion Pore Caparotta, Marcelo Rubén synaptotagmin fusion pore molecular dynamics lipids |
title_short |
The Synaptotagmin-1 C2B Domain Is a Key Regulator in the Stabilization of the Fusion Pore |
title_full |
The Synaptotagmin-1 C2B Domain Is a Key Regulator in the Stabilization of the Fusion Pore |
title_fullStr |
The Synaptotagmin-1 C2B Domain Is a Key Regulator in the Stabilization of the Fusion Pore |
title_full_unstemmed |
The Synaptotagmin-1 C2B Domain Is a Key Regulator in the Stabilization of the Fusion Pore |
title_sort |
The Synaptotagmin-1 C2B Domain Is a Key Regulator in the Stabilization of the Fusion Pore |
dc.creator.none.fl_str_mv |
Caparotta, Marcelo Rubén Tomes, Claudia Nora Mayorga, Luis Segundo Masone, Diego Fernando |
author |
Caparotta, Marcelo Rubén |
author_facet |
Caparotta, Marcelo Rubén Tomes, Claudia Nora Mayorga, Luis Segundo Masone, Diego Fernando |
author_role |
author |
author2 |
Tomes, Claudia Nora Mayorga, Luis Segundo Masone, Diego Fernando |
author2_role |
author author author |
dc.subject.none.fl_str_mv |
synaptotagmin fusion pore molecular dynamics lipids |
topic |
synaptotagmin fusion pore molecular dynamics lipids |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.2 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
Fusion pores serve as an effective mechanism to connect intracellular organelles and release vesicle contents during exocytosis. A complex lipid rearrangement takes place as membranes approximate, bend, fuse, and establish a traversing water channel to define the fusion pore, linking initially isolated chambers. Thermodynamically, the process is unfavorable and thought to be mediated by specialized proteins. In this work, we have developed a reaction coordinate to induce fusion pores from initially flat and parallel lipid bilayers and we have used it to describe the effects of the synaptotagmin-1 C2B domain during the process. We have obtained free-energy profiles of the whole lipid reorganization in biologically realistic membranes, going from planar and parallel bilayers through stalk hemifusion to water channel formation. Our results point to a lysine-rich polybasic region on synaptotagmin-1 C2B as the key to lipid reorganization control through the formation of phosphatidylinositol bisphosphate clusters that stabilize the fusion pore. Fil: Caparotta, Marcelo Rubén. Universidad Nacional de Cuyo; Argentina Fil: Tomes, Claudia Nora. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina Fil: Mayorga, Luis Segundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina Fil: Masone, Diego Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina |
description |
Fusion pores serve as an effective mechanism to connect intracellular organelles and release vesicle contents during exocytosis. A complex lipid rearrangement takes place as membranes approximate, bend, fuse, and establish a traversing water channel to define the fusion pore, linking initially isolated chambers. Thermodynamically, the process is unfavorable and thought to be mediated by specialized proteins. In this work, we have developed a reaction coordinate to induce fusion pores from initially flat and parallel lipid bilayers and we have used it to describe the effects of the synaptotagmin-1 C2B domain during the process. We have obtained free-energy profiles of the whole lipid reorganization in biologically realistic membranes, going from planar and parallel bilayers through stalk hemifusion to water channel formation. Our results point to a lysine-rich polybasic region on synaptotagmin-1 C2B as the key to lipid reorganization control through the formation of phosphatidylinositol bisphosphate clusters that stabilize the fusion pore. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-11 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/140993 Caparotta, Marcelo Rubén; Tomes, Claudia Nora; Mayorga, Luis Segundo; Masone, Diego Fernando; The Synaptotagmin-1 C2B Domain Is a Key Regulator in the Stabilization of the Fusion Pore; American Chemical Society; Journal of Chemical Theory and Computation; 16; 12; 11-2020; 7840-7851 1549-9618 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/140993 |
identifier_str_mv |
Caparotta, Marcelo Rubén; Tomes, Claudia Nora; Mayorga, Luis Segundo; Masone, Diego Fernando; The Synaptotagmin-1 C2B Domain Is a Key Regulator in the Stabilization of the Fusion Pore; American Chemical Society; Journal of Chemical Theory and Computation; 16; 12; 11-2020; 7840-7851 1549-9618 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/doi/10.1021/acs.jctc.0c00734 info:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/10.1021/acs.jctc.0c00734 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
American Chemical Society |
publisher.none.fl_str_mv |
American Chemical Society |
dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) |
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CONICET Digital (CONICET) |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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13.070432 |