Intracellular complexes of the early-onset torsion dystonia-associated AAA+ ATPase TorsinA

Autores
Li, Hui; Wu, Hui Chuan; Liu, Zhonghua; Zacchi, Lucia Florencia; Brodsky, Jeffrey L; Zolkiewski, Michal
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
A single GAG codon deletion in the gene encoding torsinA is linked to most cases of early-onset torsion dystonia. TorsinA is an ER-localized membrane-associated ATPase from the AAA+ superfamily with an unknown biological function. We investigated the formation of oligomeric complexes of torsinA in cultured mammalian cells and found that wild type torsinA associates into a complex with a molecular weight consistent with that of a homohexamer. Interestingly, the dystonia-linked variant torsinAΔE displayed a reduced propensity to form the oligomers compared to the wild type protein. We also discovered that the deletion of the N-terminal membrane-associating region of torsinA abolished oligomer formation. Our results demonstrate that the dystonia-linked mutation in the torsinA gene produces a protein variant that is deficient in maintaining its oligomeric state and suggest that ER membrane association is required to stabilize the torsinA complex.
Fil: Li, Hui. University Of Kansas; Estados Unidos
Fil: Wu, Hui Chuan. University Of Kansas; Estados Unidos
Fil: Liu, Zhonghua . University Of Kansas; Estados Unidos
Fil: Zacchi, Lucia Florencia. University Of Pittsburgh. School Of Arts And Sciences; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina
Fil: Brodsky, Jeffrey L. University Of Pittsburgh. School Of Arts And Sciences; Estados Unidos
Fil: Zolkiewski, Michal . University Of Kansas; Estados Unidos
Materia
DYSTONIA
HETEROCOMPLEXES
MUTATION
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:11336/8736
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/8736
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Intracellular complexes of the early-onset torsion dystonia-associated AAA+ ATPase TorsinALi, HuiWu, Hui ChuanLiu, Zhonghua Zacchi, Lucia FlorenciaBrodsky, Jeffrey LZolkiewski, Michal DYSTONIAHETEROCOMPLEXESMUTATIONhttps://purl.org/becyt/ford/3.4https://purl.org/becyt/ford/3A single GAG codon deletion in the gene encoding torsinA is linked to most cases of early-onset torsion dystonia. TorsinA is an ER-localized membrane-associated ATPase from the AAA+ superfamily with an unknown biological function. We investigated the formation of oligomeric complexes of torsinA in cultured mammalian cells and found that wild type torsinA associates into a complex with a molecular weight consistent with that of a homohexamer. Interestingly, the dystonia-linked variant torsinAΔE displayed a reduced propensity to form the oligomers compared to the wild type protein. We also discovered that the deletion of the N-terminal membrane-associating region of torsinA abolished oligomer formation. Our results demonstrate that the dystonia-linked mutation in the torsinA gene produces a protein variant that is deficient in maintaining its oligomeric state and suggest that ER membrane association is required to stabilize the torsinA complex.Fil: Li, Hui. University Of Kansas; Estados UnidosFil: Wu, Hui Chuan. University Of Kansas; Estados UnidosFil: Liu, Zhonghua . University Of Kansas; Estados UnidosFil: Zacchi, Lucia Florencia. University Of Pittsburgh. School Of Arts And Sciences; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; ArgentinaFil: Brodsky, Jeffrey L. University Of Pittsburgh. School Of Arts And Sciences; Estados UnidosFil: Zolkiewski, Michal . University Of Kansas; Estados UnidosSpringer2014-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/8736Li, Hui; Wu, Hui Chuan; Liu, Zhonghua ; Zacchi, Lucia Florencia; Brodsky, Jeffrey L; et al.; Intracellular complexes of the early-onset torsion dystonia-associated AAA+ ATPase TorsinA; Springer; SpringerPlus; 3; 12-2014; 7432193-1801enginfo:eu-repo/semantics/altIdentifier/url/https://springerplus.springeropen.com/articles/10.1186/2193-1801-3-743info:eu-repo/semantics/altIdentifier/doi/10.1186/2193-1801-3-743info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-11-12T09:40:37Zoai:ri.conicet.gov.ar:11336/8736instacron: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:34982025-11-12 09:40:37.306CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Intracellular complexes of the early-onset torsion dystonia-associated AAA+ ATPase TorsinA
title Intracellular complexes of the early-onset torsion dystonia-associated AAA+ ATPase TorsinA
spellingShingle Intracellular complexes of the early-onset torsion dystonia-associated AAA+ ATPase TorsinA
Li, Hui
DYSTONIA
HETEROCOMPLEXES
MUTATION
title_short Intracellular complexes of the early-onset torsion dystonia-associated AAA+ ATPase TorsinA
title_full Intracellular complexes of the early-onset torsion dystonia-associated AAA+ ATPase TorsinA
title_fullStr Intracellular complexes of the early-onset torsion dystonia-associated AAA+ ATPase TorsinA
title_full_unstemmed Intracellular complexes of the early-onset torsion dystonia-associated AAA+ ATPase TorsinA
title_sort Intracellular complexes of the early-onset torsion dystonia-associated AAA+ ATPase TorsinA
dc.creator.none.fl_str_mv Li, Hui
Wu, Hui Chuan
Liu, Zhonghua
Zacchi, Lucia Florencia
Brodsky, Jeffrey L
Zolkiewski, Michal
author Li, Hui
author_facet Li, Hui
Wu, Hui Chuan
Liu, Zhonghua
Zacchi, Lucia Florencia
Brodsky, Jeffrey L
Zolkiewski, Michal
author_role author
author2 Wu, Hui Chuan
Liu, Zhonghua
Zacchi, Lucia Florencia
Brodsky, Jeffrey L
Zolkiewski, Michal
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv DYSTONIA
HETEROCOMPLEXES
MUTATION
topic DYSTONIA
HETEROCOMPLEXES
MUTATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.4
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv A single GAG codon deletion in the gene encoding torsinA is linked to most cases of early-onset torsion dystonia. TorsinA is an ER-localized membrane-associated ATPase from the AAA+ superfamily with an unknown biological function. We investigated the formation of oligomeric complexes of torsinA in cultured mammalian cells and found that wild type torsinA associates into a complex with a molecular weight consistent with that of a homohexamer. Interestingly, the dystonia-linked variant torsinAΔE displayed a reduced propensity to form the oligomers compared to the wild type protein. We also discovered that the deletion of the N-terminal membrane-associating region of torsinA abolished oligomer formation. Our results demonstrate that the dystonia-linked mutation in the torsinA gene produces a protein variant that is deficient in maintaining its oligomeric state and suggest that ER membrane association is required to stabilize the torsinA complex.
Fil: Li, Hui. University Of Kansas; Estados Unidos
Fil: Wu, Hui Chuan. University Of Kansas; Estados Unidos
Fil: Liu, Zhonghua . University Of Kansas; Estados Unidos
Fil: Zacchi, Lucia Florencia. University Of Pittsburgh. School Of Arts And Sciences; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina
Fil: Brodsky, Jeffrey L. University Of Pittsburgh. School Of Arts And Sciences; Estados Unidos
Fil: Zolkiewski, Michal . University Of Kansas; Estados Unidos
description A single GAG codon deletion in the gene encoding torsinA is linked to most cases of early-onset torsion dystonia. TorsinA is an ER-localized membrane-associated ATPase from the AAA+ superfamily with an unknown biological function. We investigated the formation of oligomeric complexes of torsinA in cultured mammalian cells and found that wild type torsinA associates into a complex with a molecular weight consistent with that of a homohexamer. Interestingly, the dystonia-linked variant torsinAΔE displayed a reduced propensity to form the oligomers compared to the wild type protein. We also discovered that the deletion of the N-terminal membrane-associating region of torsinA abolished oligomer formation. Our results demonstrate that the dystonia-linked mutation in the torsinA gene produces a protein variant that is deficient in maintaining its oligomeric state and suggest that ER membrane association is required to stabilize the torsinA complex.
publishDate 2014
dc.date.none.fl_str_mv 2014-12
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/11336/8736
Li, Hui; Wu, Hui Chuan; Liu, Zhonghua ; Zacchi, Lucia Florencia; Brodsky, Jeffrey L; et al.; Intracellular complexes of the early-onset torsion dystonia-associated AAA+ ATPase TorsinA; Springer; SpringerPlus; 3; 12-2014; 743
2193-1801
url http://hdl.handle.net/11336/8736
identifier_str_mv Li, Hui; Wu, Hui Chuan; Liu, Zhonghua ; Zacchi, Lucia Florencia; Brodsky, Jeffrey L; et al.; Intracellular complexes of the early-onset torsion dystonia-associated AAA+ ATPase TorsinA; Springer; SpringerPlus; 3; 12-2014; 743
2193-1801
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://springerplus.springeropen.com/articles/10.1186/2193-1801-3-743
info:eu-repo/semantics/altIdentifier/doi/10.1186/2193-1801-3-743
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
dc.publisher.none.fl_str_mv Springer
publisher.none.fl_str_mv Springer
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 13.25334

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