Subunit-selective contribution to channel gating of the M4 domain of the nicotinic receptor
- Autores
- Bouzat, Cecilia Beatriz; Gumilar, Fernanda Andrea; Esandi, María del Carmen; Sine, Steve M.
- Año de publicación
- 2002
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- The muscle nicotinic receptor (AChR) is a pentamer of four different subunits, each of which contains four transmembrane domains (M1-M4). We recently showed that channel opening and closing rates of the AChR depend on a hydrogen bond involving a threonine at position 14′ of the M4 domain in the α-subunit. To determine whether residues in equivalent positions in non-α-subunits contribute to channel gating, we mutated δT14′, βT14′, and εS14′ and evaluated changes in the kinetics of acetylcholine-activated currents. The mutation εS14′A profoundly slows the rate of channel closing, an effect opposite to that produced by mutation of αT14′. Unlike mutations of αT14′, εS14′A does not affect the rate of channel opening. Mutations in δT14′ and βT14′ do not affect channel opening or closing kinetics, showing that conserved residues are not functionally equivalent in all subunits. Whereas αT14′A and εS14′A subunits contribute additively to the closing rate, they contribute nonadditively to the opening rate. Substitution of residues preserving the hydrogen bonding ability at position 14′ produce nearly normal gating kinetics. Thus, we identify subunit-specific contributions to channel gating of equivalent residues in M4 and elucidate the underlying mechanistic and structural bases.
Fil: Bouzat, Cecilia Beatriz. 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
Fil: Gumilar, Fernanda Andrea. 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
Fil: Esandi, María del Carmen. 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
Fil: Sine, Steve M.. Mayo Foundation; Estados Unidos - Materia
-
Nicotinic Receptor
Transmembrane Domains
Kinetic Analysis - 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:11336/53095
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oai:ri.conicet.gov.ar:11336/53095 |
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3498 |
network_name_str |
CONICET Digital (CONICET) |
spelling |
Subunit-selective contribution to channel gating of the M4 domain of the nicotinic receptorBouzat, Cecilia BeatrizGumilar, Fernanda AndreaEsandi, María del CarmenSine, Steve M.Nicotinic ReceptorTransmembrane DomainsKinetic Analysishttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The muscle nicotinic receptor (AChR) is a pentamer of four different subunits, each of which contains four transmembrane domains (M1-M4). We recently showed that channel opening and closing rates of the AChR depend on a hydrogen bond involving a threonine at position 14′ of the M4 domain in the α-subunit. To determine whether residues in equivalent positions in non-α-subunits contribute to channel gating, we mutated δT14′, βT14′, and εS14′ and evaluated changes in the kinetics of acetylcholine-activated currents. The mutation εS14′A profoundly slows the rate of channel closing, an effect opposite to that produced by mutation of αT14′. Unlike mutations of αT14′, εS14′A does not affect the rate of channel opening. Mutations in δT14′ and βT14′ do not affect channel opening or closing kinetics, showing that conserved residues are not functionally equivalent in all subunits. Whereas αT14′A and εS14′A subunits contribute additively to the closing rate, they contribute nonadditively to the opening rate. Substitution of residues preserving the hydrogen bonding ability at position 14′ produce nearly normal gating kinetics. Thus, we identify subunit-specific contributions to channel gating of equivalent residues in M4 and elucidate the underlying mechanistic and structural bases.Fil: Bouzat, Cecilia Beatriz. 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; ArgentinaFil: Gumilar, Fernanda Andrea. 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; ArgentinaFil: Esandi, María del Carmen. 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; ArgentinaFil: Sine, Steve M.. Mayo Foundation; Estados UnidosCell Press2002-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/53095Bouzat, Cecilia Beatriz; Gumilar, Fernanda Andrea; Esandi, María del Carmen; Sine, Steve M.; Subunit-selective contribution to channel gating of the M4 domain of the nicotinic receptor; Cell Press; Biophysical Journal; 82; 4; 4-2002; 1920-19290006-3495CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/S0006-3495(02)75541-0info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0006349502755410info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:44:38Zoai:ri.conicet.gov.ar:11336/53095instacron: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 09:44:38.638CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Subunit-selective contribution to channel gating of the M4 domain of the nicotinic receptor |
title |
Subunit-selective contribution to channel gating of the M4 domain of the nicotinic receptor |
spellingShingle |
Subunit-selective contribution to channel gating of the M4 domain of the nicotinic receptor Bouzat, Cecilia Beatriz Nicotinic Receptor Transmembrane Domains Kinetic Analysis |
title_short |
Subunit-selective contribution to channel gating of the M4 domain of the nicotinic receptor |
title_full |
Subunit-selective contribution to channel gating of the M4 domain of the nicotinic receptor |
title_fullStr |
Subunit-selective contribution to channel gating of the M4 domain of the nicotinic receptor |
title_full_unstemmed |
Subunit-selective contribution to channel gating of the M4 domain of the nicotinic receptor |
title_sort |
Subunit-selective contribution to channel gating of the M4 domain of the nicotinic receptor |
dc.creator.none.fl_str_mv |
Bouzat, Cecilia Beatriz Gumilar, Fernanda Andrea Esandi, María del Carmen Sine, Steve M. |
author |
Bouzat, Cecilia Beatriz |
author_facet |
Bouzat, Cecilia Beatriz Gumilar, Fernanda Andrea Esandi, María del Carmen Sine, Steve M. |
author_role |
author |
author2 |
Gumilar, Fernanda Andrea Esandi, María del Carmen Sine, Steve M. |
author2_role |
author author author |
dc.subject.none.fl_str_mv |
Nicotinic Receptor Transmembrane Domains Kinetic Analysis |
topic |
Nicotinic Receptor Transmembrane Domains Kinetic Analysis |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
The muscle nicotinic receptor (AChR) is a pentamer of four different subunits, each of which contains four transmembrane domains (M1-M4). We recently showed that channel opening and closing rates of the AChR depend on a hydrogen bond involving a threonine at position 14′ of the M4 domain in the α-subunit. To determine whether residues in equivalent positions in non-α-subunits contribute to channel gating, we mutated δT14′, βT14′, and εS14′ and evaluated changes in the kinetics of acetylcholine-activated currents. The mutation εS14′A profoundly slows the rate of channel closing, an effect opposite to that produced by mutation of αT14′. Unlike mutations of αT14′, εS14′A does not affect the rate of channel opening. Mutations in δT14′ and βT14′ do not affect channel opening or closing kinetics, showing that conserved residues are not functionally equivalent in all subunits. Whereas αT14′A and εS14′A subunits contribute additively to the closing rate, they contribute nonadditively to the opening rate. Substitution of residues preserving the hydrogen bonding ability at position 14′ produce nearly normal gating kinetics. Thus, we identify subunit-specific contributions to channel gating of equivalent residues in M4 and elucidate the underlying mechanistic and structural bases. Fil: Bouzat, Cecilia Beatriz. 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 Fil: Gumilar, Fernanda Andrea. 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 Fil: Esandi, María del Carmen. 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 Fil: Sine, Steve M.. Mayo Foundation; Estados Unidos |
description |
The muscle nicotinic receptor (AChR) is a pentamer of four different subunits, each of which contains four transmembrane domains (M1-M4). We recently showed that channel opening and closing rates of the AChR depend on a hydrogen bond involving a threonine at position 14′ of the M4 domain in the α-subunit. To determine whether residues in equivalent positions in non-α-subunits contribute to channel gating, we mutated δT14′, βT14′, and εS14′ and evaluated changes in the kinetics of acetylcholine-activated currents. The mutation εS14′A profoundly slows the rate of channel closing, an effect opposite to that produced by mutation of αT14′. Unlike mutations of αT14′, εS14′A does not affect the rate of channel opening. Mutations in δT14′ and βT14′ do not affect channel opening or closing kinetics, showing that conserved residues are not functionally equivalent in all subunits. Whereas αT14′A and εS14′A subunits contribute additively to the closing rate, they contribute nonadditively to the opening rate. Substitution of residues preserving the hydrogen bonding ability at position 14′ produce nearly normal gating kinetics. Thus, we identify subunit-specific contributions to channel gating of equivalent residues in M4 and elucidate the underlying mechanistic and structural bases. |
publishDate |
2002 |
dc.date.none.fl_str_mv |
2002-04 |
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/11336/53095 Bouzat, Cecilia Beatriz; Gumilar, Fernanda Andrea; Esandi, María del Carmen; Sine, Steve M.; Subunit-selective contribution to channel gating of the M4 domain of the nicotinic receptor; Cell Press; Biophysical Journal; 82; 4; 4-2002; 1920-1929 0006-3495 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/53095 |
identifier_str_mv |
Bouzat, Cecilia Beatriz; Gumilar, Fernanda Andrea; Esandi, María del Carmen; Sine, Steve M.; Subunit-selective contribution to channel gating of the M4 domain of the nicotinic receptor; Cell Press; Biophysical Journal; 82; 4; 4-2002; 1920-1929 0006-3495 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/doi/10.1016/S0006-3495(02)75541-0 info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0006349502755410 |
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 application/pdf |
dc.publisher.none.fl_str_mv |
Cell Press |
publisher.none.fl_str_mv |
Cell Press |
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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1844613404370665472 |
score |
13.070432 |