Coupling of agonist binding to channel gating in an ACh-binding protein linked to an ion channel

Autores
Bouzat, Cecilia Beatriz; Gumilar, Fernanda Andrea; Spitzmaul, Guillermo Federico; Wang, Hai Long; Rayes, Diego Hernán; Hansen, Scott B.; Taylor, Palmer; Sine, Steven M.
Año de publicación
2004
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Neurotransmitter receptors from the Cys-loop superfamily couple the binding of agonist to the opening of an intrinsic ion pore in the final step in rapid synaptic transmission. Although atomic resolution structural data have recently emerged for individual binding and pore domains how they are linked into a functional unit remains unknown. Here we identify structural requirements for functionally coupling the two domains by combining acetylcholine (ACh)-binding protein, whose structure was determined at atomic resolution, with the pore domain from the serotonin type-3A (5-HT3A) receptor. Only when amino-acid sequences of three loops in ACh-binding protein are changed to their 5-HT3A counterparts does ACh bind with low affinity characteristic of activatable receptors, and trigger opening of the ion pore. Thus functional coupling requires structural compatibility at the interface of the binding and pore domains. Structural modelling reveals a network of interacting loops between binding and pore domains that mediates this allosteric coupling process.
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: Spitzmaul, Guillermo Federico. 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: Wang, Hai Long. Mayo Clinic College of Medicine; Estados Unidos
Fil: Rayes, Diego Hernán. 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: Hansen, Scott B.. University of California at San Diego; Estados Unidos
Fil: Taylor, Palmer. University of California at San Diego; Estados Unidos
Fil: Sine, Steven M.. Mayo Clinic College of Medicine; Estados Unidos
Materia
Ach Binding Protein
Interface
Gating
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:11336/52913
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/52913
network_acronym_str CONICETDig
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network_name_str CONICET Digital (CONICET)
spelling Coupling of agonist binding to channel gating in an ACh-binding protein linked to an ion channelBouzat, Cecilia BeatrizGumilar, Fernanda AndreaSpitzmaul, Guillermo FedericoWang, Hai LongRayes, Diego HernánHansen, Scott B.Taylor, PalmerSine, Steven M.Ach Binding ProteinInterfaceGatinghttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Neurotransmitter receptors from the Cys-loop superfamily couple the binding of agonist to the opening of an intrinsic ion pore in the final step in rapid synaptic transmission. Although atomic resolution structural data have recently emerged for individual binding and pore domains how they are linked into a functional unit remains unknown. Here we identify structural requirements for functionally coupling the two domains by combining acetylcholine (ACh)-binding protein, whose structure was determined at atomic resolution, with the pore domain from the serotonin type-3A (5-HT3A) receptor. Only when amino-acid sequences of three loops in ACh-binding protein are changed to their 5-HT3A counterparts does ACh bind with low affinity characteristic of activatable receptors, and trigger opening of the ion pore. Thus functional coupling requires structural compatibility at the interface of the binding and pore domains. Structural modelling reveals a network of interacting loops between binding and pore domains that mediates this allosteric coupling process.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: Spitzmaul, Guillermo Federico. 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: Wang, Hai Long. Mayo Clinic College of Medicine; Estados UnidosFil: Rayes, Diego Hernán. 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: Hansen, Scott B.. University of California at San Diego; Estados UnidosFil: Taylor, Palmer. University of California at San Diego; Estados UnidosFil: Sine, Steven M.. Mayo Clinic College of Medicine; Estados UnidosNature Publishing Group2004-08-19info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/52913Bouzat, Cecilia Beatriz; Gumilar, Fernanda Andrea; Spitzmaul, Guillermo Federico; Wang, Hai Long; Rayes, Diego Hernán; et al.; Coupling of agonist binding to channel gating in an ACh-binding protein linked to an ion channel; Nature Publishing Group; Nature; 430; 7002; 19-8-2004; 896-9000028-08361476-4687CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/nature02753info:eu-repo/semantics/altIdentifier/doi/10.1038/nature02753info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:30:56Zoai:ri.conicet.gov.ar:11336/52913instacron: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 11:30:56.428CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Coupling of agonist binding to channel gating in an ACh-binding protein linked to an ion channel
title Coupling of agonist binding to channel gating in an ACh-binding protein linked to an ion channel
spellingShingle Coupling of agonist binding to channel gating in an ACh-binding protein linked to an ion channel
Bouzat, Cecilia Beatriz
Ach Binding Protein
Interface
Gating
title_short Coupling of agonist binding to channel gating in an ACh-binding protein linked to an ion channel
title_full Coupling of agonist binding to channel gating in an ACh-binding protein linked to an ion channel
title_fullStr Coupling of agonist binding to channel gating in an ACh-binding protein linked to an ion channel
title_full_unstemmed Coupling of agonist binding to channel gating in an ACh-binding protein linked to an ion channel
title_sort Coupling of agonist binding to channel gating in an ACh-binding protein linked to an ion channel
dc.creator.none.fl_str_mv Bouzat, Cecilia Beatriz
Gumilar, Fernanda Andrea
Spitzmaul, Guillermo Federico
Wang, Hai Long
Rayes, Diego Hernán
Hansen, Scott B.
Taylor, Palmer
Sine, Steven M.
author Bouzat, Cecilia Beatriz
author_facet Bouzat, Cecilia Beatriz
Gumilar, Fernanda Andrea
Spitzmaul, Guillermo Federico
Wang, Hai Long
Rayes, Diego Hernán
Hansen, Scott B.
Taylor, Palmer
Sine, Steven M.
author_role author
author2 Gumilar, Fernanda Andrea
Spitzmaul, Guillermo Federico
Wang, Hai Long
Rayes, Diego Hernán
Hansen, Scott B.
Taylor, Palmer
Sine, Steven M.
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Ach Binding Protein
Interface
Gating
topic Ach Binding Protein
Interface
Gating
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Neurotransmitter receptors from the Cys-loop superfamily couple the binding of agonist to the opening of an intrinsic ion pore in the final step in rapid synaptic transmission. Although atomic resolution structural data have recently emerged for individual binding and pore domains how they are linked into a functional unit remains unknown. Here we identify structural requirements for functionally coupling the two domains by combining acetylcholine (ACh)-binding protein, whose structure was determined at atomic resolution, with the pore domain from the serotonin type-3A (5-HT3A) receptor. Only when amino-acid sequences of three loops in ACh-binding protein are changed to their 5-HT3A counterparts does ACh bind with low affinity characteristic of activatable receptors, and trigger opening of the ion pore. Thus functional coupling requires structural compatibility at the interface of the binding and pore domains. Structural modelling reveals a network of interacting loops between binding and pore domains that mediates this allosteric coupling process.
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: Spitzmaul, Guillermo Federico. 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: Wang, Hai Long. Mayo Clinic College of Medicine; Estados Unidos
Fil: Rayes, Diego Hernán. 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: Hansen, Scott B.. University of California at San Diego; Estados Unidos
Fil: Taylor, Palmer. University of California at San Diego; Estados Unidos
Fil: Sine, Steven M.. Mayo Clinic College of Medicine; Estados Unidos
description Neurotransmitter receptors from the Cys-loop superfamily couple the binding of agonist to the opening of an intrinsic ion pore in the final step in rapid synaptic transmission. Although atomic resolution structural data have recently emerged for individual binding and pore domains how they are linked into a functional unit remains unknown. Here we identify structural requirements for functionally coupling the two domains by combining acetylcholine (ACh)-binding protein, whose structure was determined at atomic resolution, with the pore domain from the serotonin type-3A (5-HT3A) receptor. Only when amino-acid sequences of three loops in ACh-binding protein are changed to their 5-HT3A counterparts does ACh bind with low affinity characteristic of activatable receptors, and trigger opening of the ion pore. Thus functional coupling requires structural compatibility at the interface of the binding and pore domains. Structural modelling reveals a network of interacting loops between binding and pore domains that mediates this allosteric coupling process.
publishDate 2004
dc.date.none.fl_str_mv 2004-08-19
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/11336/52913
Bouzat, Cecilia Beatriz; Gumilar, Fernanda Andrea; Spitzmaul, Guillermo Federico; Wang, Hai Long; Rayes, Diego Hernán; et al.; Coupling of agonist binding to channel gating in an ACh-binding protein linked to an ion channel; Nature Publishing Group; Nature; 430; 7002; 19-8-2004; 896-900
0028-0836
1476-4687
CONICET Digital
CONICET
url http://hdl.handle.net/11336/52913
identifier_str_mv Bouzat, Cecilia Beatriz; Gumilar, Fernanda Andrea; Spitzmaul, Guillermo Federico; Wang, Hai Long; Rayes, Diego Hernán; et al.; Coupling of agonist binding to channel gating in an ACh-binding protein linked to an ion channel; Nature Publishing Group; Nature; 430; 7002; 19-8-2004; 896-900
0028-0836
1476-4687
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://www.nature.com/articles/nature02753
info:eu-repo/semantics/altIdentifier/doi/10.1038/nature02753
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
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
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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