The mineralocorticoid receptor forms higher order oligomers upon DNA binding

Autores
Fettweis, Gregory; Johnson, Thomas A.; Almeida Prieto, Brian; Weller Pérez, Julián; Presman, Diego Martin; Hager, Gordon L.; Alvarez de la Rosa, Diego
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The prevailing model of steroid hormone nuclear receptor function assumes ligand-induced homodimer formation followed by binding to DNA hormone response elements (HREs). This model has been challenged by evidence showing that the glucocorticoid receptor (GR) forms tetramers upon ligand and DNA binding, which then drive receptor-mediated gene transactivation and transrepression. GR and the closely-related mineralocorticoid receptors (MR) interact to transduce corticosteroid hormone signaling, but whether they share the same quaternary arrangement is unknown. Here, we used a fluorescence imaging technique, Number & Brightness, to study oligomerization in a cell system allowing real-time analysis of receptor-DNA interactions. Agonist-bound MR forms tetramers in the nucleoplasm and higher order oligomers upon binding to HREs. Antagonists form intermediate-size quaternary arrangements, suggesting that large oligomers are essential for function. Divergence between MR and GR quaternary structure is driven by different functionality of known and new multimerization interfaces, which does not preclude formation of heteromers. Thus, influencing oligomerization may be important to selectively modulate corticosteroid signaling.
Fil: Fettweis, Gregory. National Institutes of Health; Estados Unidos
Fil: Johnson, Thomas A.. National Institutes of Health; Estados Unidos
Fil: Almeida Prieto, Brian. Universidad de La Laguna; España
Fil: Weller Pérez, Julián. Universidad de La Laguna; España
Fil: Presman, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Hager, Gordon L.. National Institutes of Health; Estados Unidos
Fil: Alvarez de la Rosa, Diego. Universidad de La Laguna; España
Materia
MINERALOCORTICOID RECEPTOR
GLUCOCORTICOID RECEPTOR
OLIGOMERIZATION
NUMBER AND BRIGHTNESS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/260972
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/260972
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling The mineralocorticoid receptor forms higher order oligomers upon DNA bindingFettweis, GregoryJohnson, Thomas A.Almeida Prieto, BrianWeller Pérez, JuliánPresman, Diego MartinHager, Gordon L.Alvarez de la Rosa, DiegoMINERALOCORTICOID RECEPTORGLUCOCORTICOID RECEPTOROLIGOMERIZATIONNUMBER AND BRIGHTNESShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The prevailing model of steroid hormone nuclear receptor function assumes ligand-induced homodimer formation followed by binding to DNA hormone response elements (HREs). This model has been challenged by evidence showing that the glucocorticoid receptor (GR) forms tetramers upon ligand and DNA binding, which then drive receptor-mediated gene transactivation and transrepression. GR and the closely-related mineralocorticoid receptors (MR) interact to transduce corticosteroid hormone signaling, but whether they share the same quaternary arrangement is unknown. Here, we used a fluorescence imaging technique, Number & Brightness, to study oligomerization in a cell system allowing real-time analysis of receptor-DNA interactions. Agonist-bound MR forms tetramers in the nucleoplasm and higher order oligomers upon binding to HREs. Antagonists form intermediate-size quaternary arrangements, suggesting that large oligomers are essential for function. Divergence between MR and GR quaternary structure is driven by different functionality of known and new multimerization interfaces, which does not preclude formation of heteromers. Thus, influencing oligomerization may be important to selectively modulate corticosteroid signaling.Fil: Fettweis, Gregory. National Institutes of Health; Estados UnidosFil: Johnson, Thomas A.. National Institutes of Health; Estados UnidosFil: Almeida Prieto, Brian. Universidad de La Laguna; EspañaFil: Weller Pérez, Julián. Universidad de La Laguna; EspañaFil: Presman, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Hager, Gordon L.. National Institutes of Health; Estados UnidosFil: Alvarez de la Rosa, Diego. Universidad de La Laguna; EspañaJohn Wiley & Sons2024-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/260972Fettweis, Gregory; Johnson, Thomas A.; Almeida Prieto, Brian; Weller Pérez, Julián; Presman, Diego Martin; et al.; The mineralocorticoid receptor forms higher order oligomers upon DNA binding; John Wiley & Sons; Protein Science; 33; 3; 2-2024; 1-160961-8368CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/10.1002/pro.4890info:eu-repo/semantics/altIdentifier/doi/10.1002/pro.4890info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:45:26Zoai:ri.conicet.gov.ar:11336/260972instacron: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:34982025-09-03 09:45:26.633CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The mineralocorticoid receptor forms higher order oligomers upon DNA binding
title The mineralocorticoid receptor forms higher order oligomers upon DNA binding
spellingShingle The mineralocorticoid receptor forms higher order oligomers upon DNA binding
Fettweis, Gregory
MINERALOCORTICOID RECEPTOR
GLUCOCORTICOID RECEPTOR
OLIGOMERIZATION
NUMBER AND BRIGHTNESS
title_short The mineralocorticoid receptor forms higher order oligomers upon DNA binding
title_full The mineralocorticoid receptor forms higher order oligomers upon DNA binding
title_fullStr The mineralocorticoid receptor forms higher order oligomers upon DNA binding
title_full_unstemmed The mineralocorticoid receptor forms higher order oligomers upon DNA binding
title_sort The mineralocorticoid receptor forms higher order oligomers upon DNA binding
dc.creator.none.fl_str_mv Fettweis, Gregory
Johnson, Thomas A.
Almeida Prieto, Brian
Weller Pérez, Julián
Presman, Diego Martin
Hager, Gordon L.
Alvarez de la Rosa, Diego
author Fettweis, Gregory
author_facet Fettweis, Gregory
Johnson, Thomas A.
Almeida Prieto, Brian
Weller Pérez, Julián
Presman, Diego Martin
Hager, Gordon L.
Alvarez de la Rosa, Diego
author_role author
author2 Johnson, Thomas A.
Almeida Prieto, Brian
Weller Pérez, Julián
Presman, Diego Martin
Hager, Gordon L.
Alvarez de la Rosa, Diego
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv MINERALOCORTICOID RECEPTOR
GLUCOCORTICOID RECEPTOR
OLIGOMERIZATION
NUMBER AND BRIGHTNESS
topic MINERALOCORTICOID RECEPTOR
GLUCOCORTICOID RECEPTOR
OLIGOMERIZATION
NUMBER AND BRIGHTNESS
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 prevailing model of steroid hormone nuclear receptor function assumes ligand-induced homodimer formation followed by binding to DNA hormone response elements (HREs). This model has been challenged by evidence showing that the glucocorticoid receptor (GR) forms tetramers upon ligand and DNA binding, which then drive receptor-mediated gene transactivation and transrepression. GR and the closely-related mineralocorticoid receptors (MR) interact to transduce corticosteroid hormone signaling, but whether they share the same quaternary arrangement is unknown. Here, we used a fluorescence imaging technique, Number & Brightness, to study oligomerization in a cell system allowing real-time analysis of receptor-DNA interactions. Agonist-bound MR forms tetramers in the nucleoplasm and higher order oligomers upon binding to HREs. Antagonists form intermediate-size quaternary arrangements, suggesting that large oligomers are essential for function. Divergence between MR and GR quaternary structure is driven by different functionality of known and new multimerization interfaces, which does not preclude formation of heteromers. Thus, influencing oligomerization may be important to selectively modulate corticosteroid signaling.
Fil: Fettweis, Gregory. National Institutes of Health; Estados Unidos
Fil: Johnson, Thomas A.. National Institutes of Health; Estados Unidos
Fil: Almeida Prieto, Brian. Universidad de La Laguna; España
Fil: Weller Pérez, Julián. Universidad de La Laguna; España
Fil: Presman, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Hager, Gordon L.. National Institutes of Health; Estados Unidos
Fil: Alvarez de la Rosa, Diego. Universidad de La Laguna; España
description The prevailing model of steroid hormone nuclear receptor function assumes ligand-induced homodimer formation followed by binding to DNA hormone response elements (HREs). This model has been challenged by evidence showing that the glucocorticoid receptor (GR) forms tetramers upon ligand and DNA binding, which then drive receptor-mediated gene transactivation and transrepression. GR and the closely-related mineralocorticoid receptors (MR) interact to transduce corticosteroid hormone signaling, but whether they share the same quaternary arrangement is unknown. Here, we used a fluorescence imaging technique, Number & Brightness, to study oligomerization in a cell system allowing real-time analysis of receptor-DNA interactions. Agonist-bound MR forms tetramers in the nucleoplasm and higher order oligomers upon binding to HREs. Antagonists form intermediate-size quaternary arrangements, suggesting that large oligomers are essential for function. Divergence between MR and GR quaternary structure is driven by different functionality of known and new multimerization interfaces, which does not preclude formation of heteromers. Thus, influencing oligomerization may be important to selectively modulate corticosteroid signaling.
publishDate 2024
dc.date.none.fl_str_mv 2024-02
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/11336/260972
Fettweis, Gregory; Johnson, Thomas A.; Almeida Prieto, Brian; Weller Pérez, Julián; Presman, Diego Martin; et al.; The mineralocorticoid receptor forms higher order oligomers upon DNA binding; John Wiley & Sons; Protein Science; 33; 3; 2-2024; 1-16
0961-8368
CONICET Digital
CONICET
url http://hdl.handle.net/11336/260972
identifier_str_mv Fettweis, Gregory; Johnson, Thomas A.; Almeida Prieto, Brian; Weller Pérez, Julián; Presman, Diego Martin; et al.; The mineralocorticoid receptor forms higher order oligomers upon DNA binding; John Wiley & Sons; Protein Science; 33; 3; 2-2024; 1-16
0961-8368
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://onlinelibrary.wiley.com/doi/10.1002/pro.4890
info:eu-repo/semantics/altIdentifier/doi/10.1002/pro.4890
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv John Wiley & Sons
publisher.none.fl_str_mv John Wiley & Sons
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_ 1842268730983186432
score 13.13397

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