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
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/174939
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/174939
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling 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 Técnicas2025-10-22T11:08:18Zoai: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:34982025-10-22 11:08:19.292CONICET 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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score 12.982451

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