Synaptotagmin-1 C2B domains cooperatively stabilize the fusion stalk via a master-servant mechanism
- Autores
- Di Bartolo, Ary Lautaro; Masone, Diego Fernando
- Año de publicación
- 2022
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Synaptotagmin-1 is a low-affinity Ca2+ sensor that triggers synchronous vesicle fusion. It contains two similar C2 domains (C2A and C2B) that cooperate in membrane binding, being the C2B domain mainly responsible for the membrane fusion process due to its polybasic patch KRLKKKKTTIKK (321-332). In this work, a master-servant mechanism between two identical C2B domains is shown to control the formation of the fusion stalk in a calcium-independent manner. Two regions in C2B are essential for the process, the well-known polybasic patch and a recently described pair of arginines (398 399). The master domain shows strong PIP2 interactions with its polybasic patch and its pair of arginines. At the same time, the servant analogously cooperates with the master to reduce the total work to form the fusion stalk. The strategic mutation (T328E, T329E) in both master and servant domains disrupts the cooperative mechanism, drastically increasing the free energy needed to induce the fusion stalk, however, with negligible effects on the master domain interactions with PIP2. These data point to a difference in the behavior of the servant domain, which is unable to sustain its PIP2 interactions neither through its polybasic patch nor through its pair of arginines, and in the end, losing its ability to assist the master in the formation of the fusion stalk.
Fil: Di Bartolo, Ary Lautaro. 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. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales; 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. Universidad Nacional de Cuyo. Facultad de Ingeniería; Argentina - Materia
-
FUSION STALK
MOLECULAR DYNAMICS
HPC
SYNAPTOTAGMIN-1 - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/204697
Ver los metadatos del registro completo
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network_name_str |
CONICET Digital (CONICET) |
spelling |
Synaptotagmin-1 C2B domains cooperatively stabilize the fusion stalk via a master-servant mechanismDi Bartolo, Ary LautaroMasone, Diego FernandoFUSION STALKMOLECULAR DYNAMICSHPCSYNAPTOTAGMIN-1https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Synaptotagmin-1 is a low-affinity Ca2+ sensor that triggers synchronous vesicle fusion. It contains two similar C2 domains (C2A and C2B) that cooperate in membrane binding, being the C2B domain mainly responsible for the membrane fusion process due to its polybasic patch KRLKKKKTTIKK (321-332). In this work, a master-servant mechanism between two identical C2B domains is shown to control the formation of the fusion stalk in a calcium-independent manner. Two regions in C2B are essential for the process, the well-known polybasic patch and a recently described pair of arginines (398 399). The master domain shows strong PIP2 interactions with its polybasic patch and its pair of arginines. At the same time, the servant analogously cooperates with the master to reduce the total work to form the fusion stalk. The strategic mutation (T328E, T329E) in both master and servant domains disrupts the cooperative mechanism, drastically increasing the free energy needed to induce the fusion stalk, however, with negligible effects on the master domain interactions with PIP2. These data point to a difference in the behavior of the servant domain, which is unable to sustain its PIP2 interactions neither through its polybasic patch nor through its pair of arginines, and in the end, losing its ability to assist the master in the formation of the fusion stalk.Fil: Di Bartolo, Ary Lautaro. 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. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales; 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; Argentina. Universidad Nacional de Cuyo. Facultad de Ingeniería; ArgentinaRoyal Society of Chemistry2022-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/204697Di Bartolo, Ary Lautaro; Masone, Diego Fernando; Synaptotagmin-1 C2B domains cooperatively stabilize the fusion stalk via a master-servant mechanism; Royal Society of Chemistry; Chemical Science; 13; 12; 2-2022; 3437-34462041-65202041-6539CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://pubs.rsc.org/en/Content/ArticleLanding/2022/SC/D1SC06711Ginfo:eu-repo/semantics/altIdentifier/doi/10.1039/D1SC06711Ginfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:28:25Zoai:ri.conicet.gov.ar:11336/204697instacron: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:34982025-10-15 14:28:25.545CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Synaptotagmin-1 C2B domains cooperatively stabilize the fusion stalk via a master-servant mechanism |
title |
Synaptotagmin-1 C2B domains cooperatively stabilize the fusion stalk via a master-servant mechanism |
spellingShingle |
Synaptotagmin-1 C2B domains cooperatively stabilize the fusion stalk via a master-servant mechanism Di Bartolo, Ary Lautaro FUSION STALK MOLECULAR DYNAMICS HPC SYNAPTOTAGMIN-1 |
title_short |
Synaptotagmin-1 C2B domains cooperatively stabilize the fusion stalk via a master-servant mechanism |
title_full |
Synaptotagmin-1 C2B domains cooperatively stabilize the fusion stalk via a master-servant mechanism |
title_fullStr |
Synaptotagmin-1 C2B domains cooperatively stabilize the fusion stalk via a master-servant mechanism |
title_full_unstemmed |
Synaptotagmin-1 C2B domains cooperatively stabilize the fusion stalk via a master-servant mechanism |
title_sort |
Synaptotagmin-1 C2B domains cooperatively stabilize the fusion stalk via a master-servant mechanism |
dc.creator.none.fl_str_mv |
Di Bartolo, Ary Lautaro Masone, Diego Fernando |
author |
Di Bartolo, Ary Lautaro |
author_facet |
Di Bartolo, Ary Lautaro Masone, Diego Fernando |
author_role |
author |
author2 |
Masone, Diego Fernando |
author2_role |
author |
dc.subject.none.fl_str_mv |
FUSION STALK MOLECULAR DYNAMICS HPC SYNAPTOTAGMIN-1 |
topic |
FUSION STALK MOLECULAR DYNAMICS HPC SYNAPTOTAGMIN-1 |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
Synaptotagmin-1 is a low-affinity Ca2+ sensor that triggers synchronous vesicle fusion. It contains two similar C2 domains (C2A and C2B) that cooperate in membrane binding, being the C2B domain mainly responsible for the membrane fusion process due to its polybasic patch KRLKKKKTTIKK (321-332). In this work, a master-servant mechanism between two identical C2B domains is shown to control the formation of the fusion stalk in a calcium-independent manner. Two regions in C2B are essential for the process, the well-known polybasic patch and a recently described pair of arginines (398 399). The master domain shows strong PIP2 interactions with its polybasic patch and its pair of arginines. At the same time, the servant analogously cooperates with the master to reduce the total work to form the fusion stalk. The strategic mutation (T328E, T329E) in both master and servant domains disrupts the cooperative mechanism, drastically increasing the free energy needed to induce the fusion stalk, however, with negligible effects on the master domain interactions with PIP2. These data point to a difference in the behavior of the servant domain, which is unable to sustain its PIP2 interactions neither through its polybasic patch nor through its pair of arginines, and in the end, losing its ability to assist the master in the formation of the fusion stalk. Fil: Di Bartolo, Ary Lautaro. 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. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales; 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. Universidad Nacional de Cuyo. Facultad de Ingeniería; Argentina |
description |
Synaptotagmin-1 is a low-affinity Ca2+ sensor that triggers synchronous vesicle fusion. It contains two similar C2 domains (C2A and C2B) that cooperate in membrane binding, being the C2B domain mainly responsible for the membrane fusion process due to its polybasic patch KRLKKKKTTIKK (321-332). In this work, a master-servant mechanism between two identical C2B domains is shown to control the formation of the fusion stalk in a calcium-independent manner. Two regions in C2B are essential for the process, the well-known polybasic patch and a recently described pair of arginines (398 399). The master domain shows strong PIP2 interactions with its polybasic patch and its pair of arginines. At the same time, the servant analogously cooperates with the master to reduce the total work to form the fusion stalk. The strategic mutation (T328E, T329E) in both master and servant domains disrupts the cooperative mechanism, drastically increasing the free energy needed to induce the fusion stalk, however, with negligible effects on the master domain interactions with PIP2. These data point to a difference in the behavior of the servant domain, which is unable to sustain its PIP2 interactions neither through its polybasic patch nor through its pair of arginines, and in the end, losing its ability to assist the master in the formation of the fusion stalk. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-02 |
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/11336/204697 Di Bartolo, Ary Lautaro; Masone, Diego Fernando; Synaptotagmin-1 C2B domains cooperatively stabilize the fusion stalk via a master-servant mechanism; Royal Society of Chemistry; Chemical Science; 13; 12; 2-2022; 3437-3446 2041-6520 2041-6539 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/204697 |
identifier_str_mv |
Di Bartolo, Ary Lautaro; Masone, Diego Fernando; Synaptotagmin-1 C2B domains cooperatively stabilize the fusion stalk via a master-servant mechanism; Royal Society of Chemistry; Chemical Science; 13; 12; 2-2022; 3437-3446 2041-6520 2041-6539 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/url/http://pubs.rsc.org/en/Content/ArticleLanding/2022/SC/D1SC06711G info:eu-repo/semantics/altIdentifier/doi/10.1039/D1SC06711G |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Royal Society of Chemistry |
publisher.none.fl_str_mv |
Royal Society of Chemistry |
dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
reponame_str |
CONICET Digital (CONICET) |
collection |
CONICET Digital (CONICET) |
instname_str |
Consejo Nacional de Investigaciones Científicas y Técnicas |
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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1846082747301363712 |
score |
13.22299 |