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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/52913
Ver los metadatos del registro completo
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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 Técnicas2025-09-29T10:01:24Zoai: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:34982025-09-29 10:01:24.851CONICET 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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1844613807342616576 |
score |
13.070432 |