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
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/53095
Acceder
id CONICETDig_37dd6d85a020a1de0c968f13c4a021aa
oai_identifier_str oai:ri.conicet.gov.ar:11336/53095
network_acronym_str CONICETDig
repository_id_str 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 Técnicas2025-10-22T11:13:28Zoai: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:34982025-10-22 11:13:28.281CONICET 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
_version_ 1846781542783778816
score 12.982451

Publicaciones similares