The Synaptotagmin-1 C2B Domain Is a Key Regulator in the Stabilization of the Fusion Pore

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 isola...

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Detalles Bibliográficos
Autores: Caparotta, Marcelo Rubén, Tomes, Claudia Nora, Mayorga, Luis Segundo, Masone, Diego Fernando
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/140993
Acceso en línea:http://hdl.handle.net/11336/140993
Access Level:acceso abierto
Palabra clave:synaptotagmin
fusion pore
molecular dynamics
lipids
https://purl.org/becyt/ford/1.2
https://purl.org/becyt/ford/1
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spelling 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 Técnicas2024-05-08T14:28:14Zoai: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:34982024-05-08 14:28:14.887CONICET 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
https://purl.org/becyt/ford/1.2
https://purl.org/becyt/ford/1
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
https://purl.org/becyt/ford/1.2
https://purl.org/becyt/ford/1
topic synaptotagmin
fusion pore
molecular dynamics
lipids
https://purl.org/becyt/ford/1.2
https://purl.org/becyt/ford/1
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
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
repository.name.fl_str_mv 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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score 15.812429

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