Atomistic Molecular Dynamics Simulations of α7 nAChR Interacting with Cholesterol and Cholestenone in Lipid Membranes

Autores
Vietri, Agustin; Obiol, Diego Javier; Amundarain, María Julia; Antollini, Silvia Susana; Costabel, Marcelo Daniel
Año de publicación
2024
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels composed of five transmembrane glycoprotein subunits arranged pseudosymmetrically around a central pore or channel. These receptors can adopt three main conformational states, in addition to several intermediate states: a closed or resting state, an open state upon agonist binding, and a desensitized state after prolonged presence of the agonist. nAChRs are sensitive to their lipid environment, meaning that even subtle changes in the surrounding lipids can significantly impact their activity and, consequently, human biology. The lipids near the receptor can be located in annular or non-annular sites; non- annular sites are in close contact with the receptor and have a low replacement rate, while annular sites are farther and have a higher replacement rate. In this study, we focused on the relationship between nAChRs and their surrounding membrane environment. A receptor model based on a known structure (PDB: 7EKI) was embedded in lipid bilayers with varying lipids compositions in order to modify the nAChR lipid environment. The membranes consisted of POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine), cholesterol and cholestenone, the latter being a product of cholesterol oxidation and isomerization catalyzed by cholesterol oxidase. Atomistic Molecular Dynamics simulations were conducted using GROMACS2021 and CHARMM36 force field. Interactions between cholesterol/cholestenone molecules and the homomeric α7 nAChR model were examined, focusing on the transmembrane domain (TMD) of the receptor. Differences in how these lipids interact with nAChRs were observed, with cholestenone molecules locating closer to TMD than cholesterol molecules. This analysis suggests that variations in the ratio of these lipids within the membrane may cause changes in nAChR modulation.
Fil: Vietri, Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; Argentina
Fil: Obiol, Diego Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; Argentina
Fil: Amundarain, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; Argentina
Fil: Antollini, Silvia Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Costabel, Marcelo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; Argentina
LII Reunión Anual de la Sociedad Argentina de Biofísica
Bahía Blanca
Argentina
Sociedad Argentina de Biofísica
Materia
nicotinic acetylcholine receptor
cholesterol
cholesterone
model system
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:11336/277541
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Atomistic Molecular Dynamics Simulations of α7 nAChR Interacting with Cholesterol and Cholestenone in Lipid MembranesVietri, AgustinObiol, Diego JavierAmundarain, María JuliaAntollini, Silvia SusanaCostabel, Marcelo Danielnicotinic acetylcholine receptorcholesterolcholesteronemodel systemhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels composed of five transmembrane glycoprotein subunits arranged pseudosymmetrically around a central pore or channel. These receptors can adopt three main conformational states, in addition to several intermediate states: a closed or resting state, an open state upon agonist binding, and a desensitized state after prolonged presence of the agonist. nAChRs are sensitive to their lipid environment, meaning that even subtle changes in the surrounding lipids can significantly impact their activity and, consequently, human biology. The lipids near the receptor can be located in annular or non-annular sites; non- annular sites are in close contact with the receptor and have a low replacement rate, while annular sites are farther and have a higher replacement rate. In this study, we focused on the relationship between nAChRs and their surrounding membrane environment. A receptor model based on a known structure (PDB: 7EKI) was embedded in lipid bilayers with varying lipids compositions in order to modify the nAChR lipid environment. The membranes consisted of POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine), cholesterol and cholestenone, the latter being a product of cholesterol oxidation and isomerization catalyzed by cholesterol oxidase. Atomistic Molecular Dynamics simulations were conducted using GROMACS2021 and CHARMM36 force field. Interactions between cholesterol/cholestenone molecules and the homomeric α7 nAChR model were examined, focusing on the transmembrane domain (TMD) of the receptor. Differences in how these lipids interact with nAChRs were observed, with cholestenone molecules locating closer to TMD than cholesterol molecules. This analysis suggests that variations in the ratio of these lipids within the membrane may cause changes in nAChR modulation.Fil: Vietri, Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; ArgentinaFil: Obiol, Diego Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; ArgentinaFil: Amundarain, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; ArgentinaFil: Antollini, Silvia Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Costabel, Marcelo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; ArgentinaLII Reunión Anual de la Sociedad Argentina de BiofísicaBahía BlancaArgentinaSociedad Argentina de BiofísicaSociedad Argentina de BiofísicaRivas, Gabriela LeonorVázquez, Diego EduardoCelej, Maria Soledad2024info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/277541Atomistic Molecular Dynamics Simulations of α7 nAChR Interacting with Cholesterol and Cholestenone in Lipid Membranes; LII Reunión Anual de la Sociedad Argentina de Biofísica; Bahía Blanca; Argentina; 2024; 76-76978-987-48938-2-6CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://biofisica.org.ar/publicaciones/libros-de-resumenes/Nacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-12-23T13:51:19Zoai:ri.conicet.gov.ar:11336/277541instacron: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:34982025-12-23 13:51:19.662CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Atomistic Molecular Dynamics Simulations of α7 nAChR Interacting with Cholesterol and Cholestenone in Lipid Membranes
title Atomistic Molecular Dynamics Simulations of α7 nAChR Interacting with Cholesterol and Cholestenone in Lipid Membranes
spellingShingle Atomistic Molecular Dynamics Simulations of α7 nAChR Interacting with Cholesterol and Cholestenone in Lipid Membranes
Vietri, Agustin
nicotinic acetylcholine receptor
cholesterol
cholesterone
model system
title_short Atomistic Molecular Dynamics Simulations of α7 nAChR Interacting with Cholesterol and Cholestenone in Lipid Membranes
title_full Atomistic Molecular Dynamics Simulations of α7 nAChR Interacting with Cholesterol and Cholestenone in Lipid Membranes
title_fullStr Atomistic Molecular Dynamics Simulations of α7 nAChR Interacting with Cholesterol and Cholestenone in Lipid Membranes
title_full_unstemmed Atomistic Molecular Dynamics Simulations of α7 nAChR Interacting with Cholesterol and Cholestenone in Lipid Membranes
title_sort Atomistic Molecular Dynamics Simulations of α7 nAChR Interacting with Cholesterol and Cholestenone in Lipid Membranes
dc.creator.none.fl_str_mv Vietri, Agustin
Obiol, Diego Javier
Amundarain, María Julia
Antollini, Silvia Susana
Costabel, Marcelo Daniel
author Vietri, Agustin
author_facet Vietri, Agustin
Obiol, Diego Javier
Amundarain, María Julia
Antollini, Silvia Susana
Costabel, Marcelo Daniel
author_role author
author2 Obiol, Diego Javier
Amundarain, María Julia
Antollini, Silvia Susana
Costabel, Marcelo Daniel
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Rivas, Gabriela Leonor
Vázquez, Diego Eduardo
Celej, Maria Soledad
dc.subject.none.fl_str_mv nicotinic acetylcholine receptor
cholesterol
cholesterone
model system
topic nicotinic acetylcholine receptor
cholesterol
cholesterone
model system
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels composed of five transmembrane glycoprotein subunits arranged pseudosymmetrically around a central pore or channel. These receptors can adopt three main conformational states, in addition to several intermediate states: a closed or resting state, an open state upon agonist binding, and a desensitized state after prolonged presence of the agonist. nAChRs are sensitive to their lipid environment, meaning that even subtle changes in the surrounding lipids can significantly impact their activity and, consequently, human biology. The lipids near the receptor can be located in annular or non-annular sites; non- annular sites are in close contact with the receptor and have a low replacement rate, while annular sites are farther and have a higher replacement rate. In this study, we focused on the relationship between nAChRs and their surrounding membrane environment. A receptor model based on a known structure (PDB: 7EKI) was embedded in lipid bilayers with varying lipids compositions in order to modify the nAChR lipid environment. The membranes consisted of POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine), cholesterol and cholestenone, the latter being a product of cholesterol oxidation and isomerization catalyzed by cholesterol oxidase. Atomistic Molecular Dynamics simulations were conducted using GROMACS2021 and CHARMM36 force field. Interactions between cholesterol/cholestenone molecules and the homomeric α7 nAChR model were examined, focusing on the transmembrane domain (TMD) of the receptor. Differences in how these lipids interact with nAChRs were observed, with cholestenone molecules locating closer to TMD than cholesterol molecules. This analysis suggests that variations in the ratio of these lipids within the membrane may cause changes in nAChR modulation.
Fil: Vietri, Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; Argentina
Fil: Obiol, Diego Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; Argentina
Fil: Amundarain, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; Argentina
Fil: Antollini, Silvia Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Costabel, Marcelo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; Argentina
LII Reunión Anual de la Sociedad Argentina de Biofísica
Bahía Blanca
Argentina
Sociedad Argentina de Biofísica
description Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels composed of five transmembrane glycoprotein subunits arranged pseudosymmetrically around a central pore or channel. These receptors can adopt three main conformational states, in addition to several intermediate states: a closed or resting state, an open state upon agonist binding, and a desensitized state after prolonged presence of the agonist. nAChRs are sensitive to their lipid environment, meaning that even subtle changes in the surrounding lipids can significantly impact their activity and, consequently, human biology. The lipids near the receptor can be located in annular or non-annular sites; non- annular sites are in close contact with the receptor and have a low replacement rate, while annular sites are farther and have a higher replacement rate. In this study, we focused on the relationship between nAChRs and their surrounding membrane environment. A receptor model based on a known structure (PDB: 7EKI) was embedded in lipid bilayers with varying lipids compositions in order to modify the nAChR lipid environment. The membranes consisted of POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine), cholesterol and cholestenone, the latter being a product of cholesterol oxidation and isomerization catalyzed by cholesterol oxidase. Atomistic Molecular Dynamics simulations were conducted using GROMACS2021 and CHARMM36 force field. Interactions between cholesterol/cholestenone molecules and the homomeric α7 nAChR model were examined, focusing on the transmembrane domain (TMD) of the receptor. Differences in how these lipids interact with nAChRs were observed, with cholestenone molecules locating closer to TMD than cholesterol molecules. This analysis suggests that variations in the ratio of these lipids within the membrane may cause changes in nAChR modulation.
publishDate 2024
dc.date.none.fl_str_mv 2024
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Congreso
Book
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/277541
Atomistic Molecular Dynamics Simulations of α7 nAChR Interacting with Cholesterol and Cholestenone in Lipid Membranes; LII Reunión Anual de la Sociedad Argentina de Biofísica; Bahía Blanca; Argentina; 2024; 76-76
978-987-48938-2-6
CONICET Digital
CONICET
url http://hdl.handle.net/11336/277541
identifier_str_mv Atomistic Molecular Dynamics Simulations of α7 nAChR Interacting with Cholesterol and Cholestenone in Lipid Membranes; LII Reunión Anual de la Sociedad Argentina de Biofísica; Bahía Blanca; Argentina; 2024; 76-76
978-987-48938-2-6
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://biofisica.org.ar/publicaciones/libros-de-resumenes/
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
application/pdf
dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Sociedad Argentina de Biofísica
publisher.none.fl_str_mv Sociedad Argentina de Biofísica
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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