Positively charged residues in the head domain of P2X4 receptors assist the binding of ATP
- Autores
- Racigh, Vanesa Elizabeth; Ormazábal, Agustín; Palma, Juliana Isabel; Pierdominici Sottile, Gustavo
- Año de publicación
- 2019
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- P2X receptors are a family of trimeric cationic channels located in the membrane of mammalian cells. They open in response to the binding of ATP. The differences between the closed and open structures have been described in detail for some members of the family. However, the order in which the conformational changes take place as ATP enters the binding cleft, and the residues involved in the intermediate stages, are still unknown. Here, we present the results of umbrella sampling simulations aimed to elucidate the sequence of conformational changes that occur during the reversible binding of ATP to the P2X4 receptor. The simulations also provided information about the interactions that develop in the course of the process. In particular, they revealed the existence of a metastable state which assists the binding. This state is stabilized by positively charged residues located in the head domain of the receptor. Based on these findings, we propose a novel mechanism for the capture of ATP by P2X4 receptors.
Fil: Racigh, Vanesa Elizabeth. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Ormazábal, Agustín. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Palma, Juliana Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina
Fil: Pierdominici Sottile, Gustavo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina - Materia
-
Molecular Dynamics
P2X Receptors
Umbrella Sampling - 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:11336/174939
Ver los metadatos del registro completo
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Positively charged residues in the head domain of P2X4 receptors assist the binding of ATPRacigh, Vanesa ElizabethOrmazábal, AgustínPalma, Juliana IsabelPierdominici Sottile, GustavoMolecular DynamicsP2X ReceptorsUmbrella Samplinghttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1P2X receptors are a family of trimeric cationic channels located in the membrane of mammalian cells. They open in response to the binding of ATP. The differences between the closed and open structures have been described in detail for some members of the family. However, the order in which the conformational changes take place as ATP enters the binding cleft, and the residues involved in the intermediate stages, are still unknown. Here, we present the results of umbrella sampling simulations aimed to elucidate the sequence of conformational changes that occur during the reversible binding of ATP to the P2X4 receptor. The simulations also provided information about the interactions that develop in the course of the process. In particular, they revealed the existence of a metastable state which assists the binding. This state is stabilized by positively charged residues located in the head domain of the receptor. Based on these findings, we propose a novel mechanism for the capture of ATP by P2X4 receptors.Fil: Racigh, Vanesa Elizabeth. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ormazábal, Agustín. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Palma, Juliana Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; ArgentinaFil: Pierdominici Sottile, Gustavo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaAmerican Chemical Society2019-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/174939Racigh, Vanesa Elizabeth; Ormazábal, Agustín; Palma, Juliana Isabel; Pierdominici Sottile, Gustavo; Positively charged residues in the head domain of P2X4 receptors assist the binding of ATP; American Chemical Society; Journal of Chemical Information and Modeling; 60; 2; 11-2019; 923-9321549-9596CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/abs/10.1021/acs.jcim.9b00856info:eu-repo/semantics/altIdentifier/doi/10.1021/acs.jcim.9b00856info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:39:54Zoai:ri.conicet.gov.ar:11336/174939instacron: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 09:39:54.7CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Positively charged residues in the head domain of P2X4 receptors assist the binding of ATP |
title |
Positively charged residues in the head domain of P2X4 receptors assist the binding of ATP |
spellingShingle |
Positively charged residues in the head domain of P2X4 receptors assist the binding of ATP Racigh, Vanesa Elizabeth Molecular Dynamics P2X Receptors Umbrella Sampling |
title_short |
Positively charged residues in the head domain of P2X4 receptors assist the binding of ATP |
title_full |
Positively charged residues in the head domain of P2X4 receptors assist the binding of ATP |
title_fullStr |
Positively charged residues in the head domain of P2X4 receptors assist the binding of ATP |
title_full_unstemmed |
Positively charged residues in the head domain of P2X4 receptors assist the binding of ATP |
title_sort |
Positively charged residues in the head domain of P2X4 receptors assist the binding of ATP |
dc.creator.none.fl_str_mv |
Racigh, Vanesa Elizabeth Ormazábal, Agustín Palma, Juliana Isabel Pierdominici Sottile, Gustavo |
author |
Racigh, Vanesa Elizabeth |
author_facet |
Racigh, Vanesa Elizabeth Ormazábal, Agustín Palma, Juliana Isabel Pierdominici Sottile, Gustavo |
author_role |
author |
author2 |
Ormazábal, Agustín Palma, Juliana Isabel Pierdominici Sottile, Gustavo |
author2_role |
author author author |
dc.subject.none.fl_str_mv |
Molecular Dynamics P2X Receptors Umbrella Sampling |
topic |
Molecular Dynamics P2X Receptors Umbrella Sampling |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.4 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
P2X receptors are a family of trimeric cationic channels located in the membrane of mammalian cells. They open in response to the binding of ATP. The differences between the closed and open structures have been described in detail for some members of the family. However, the order in which the conformational changes take place as ATP enters the binding cleft, and the residues involved in the intermediate stages, are still unknown. Here, we present the results of umbrella sampling simulations aimed to elucidate the sequence of conformational changes that occur during the reversible binding of ATP to the P2X4 receptor. The simulations also provided information about the interactions that develop in the course of the process. In particular, they revealed the existence of a metastable state which assists the binding. This state is stabilized by positively charged residues located in the head domain of the receptor. Based on these findings, we propose a novel mechanism for the capture of ATP by P2X4 receptors. Fil: Racigh, Vanesa Elizabeth. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Ormazábal, Agustín. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Palma, Juliana Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina Fil: Pierdominici Sottile, Gustavo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina |
description |
P2X receptors are a family of trimeric cationic channels located in the membrane of mammalian cells. They open in response to the binding of ATP. The differences between the closed and open structures have been described in detail for some members of the family. However, the order in which the conformational changes take place as ATP enters the binding cleft, and the residues involved in the intermediate stages, are still unknown. Here, we present the results of umbrella sampling simulations aimed to elucidate the sequence of conformational changes that occur during the reversible binding of ATP to the P2X4 receptor. The simulations also provided information about the interactions that develop in the course of the process. In particular, they revealed the existence of a metastable state which assists the binding. This state is stabilized by positively charged residues located in the head domain of the receptor. Based on these findings, we propose a novel mechanism for the capture of ATP by P2X4 receptors. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-11 |
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/11336/174939 Racigh, Vanesa Elizabeth; Ormazábal, Agustín; Palma, Juliana Isabel; Pierdominici Sottile, Gustavo; Positively charged residues in the head domain of P2X4 receptors assist the binding of ATP; American Chemical Society; Journal of Chemical Information and Modeling; 60; 2; 11-2019; 923-932 1549-9596 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/174939 |
identifier_str_mv |
Racigh, Vanesa Elizabeth; Ormazábal, Agustín; Palma, Juliana Isabel; Pierdominici Sottile, Gustavo; Positively charged residues in the head domain of P2X4 receptors assist the binding of ATP; American Chemical Society; Journal of Chemical Information and Modeling; 60; 2; 11-2019; 923-932 1549-9596 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/abs/10.1021/acs.jcim.9b00856 info:eu-repo/semantics/altIdentifier/doi/10.1021/acs.jcim.9b00856 |
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 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 |
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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13.070432 |