Thermodynamics of protein destabilization in live cells

Autores
Danielsson, Jens; Mu, Xin; Lang, Lisa; Wang, Huabing; Binolfi, Andrés; Theillet, François Xavier; Bekei, Beata; Logan, Derek T.; Selenko, Philipp; Wennerström, Håkan; Oliveberg, Mikael
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Although protein folding and stability have been well explored under simplified conditions in vitro, it is yet unclear how these basic self-organization events are modulated by the crowded interior of live cells. To find out, we use here in-cell NMR to follow at atomic resolution the thermal unfolding of a ß-barrel protein inside mammalian and bacterial cells. Challenging the view from in vitro crowding effects, we find that the cells destabilize the protein at 37°C but with a conspicuous twist While the melting temperature goes down the cold unfolding moves into the physiological regime, coupled to an augmented heat-capacity change. The effect seems induced by transient, sequence-specific, interactions with the cellular components, acting preferentially on the unfolded ensemble. This points to a model where the in vivo influence on protein behavior is case specific, determined by the individual protein's interplay with the functionally optimized "interaction landscape" of the cellular interior.
Fil: Danielsson, Jens. Stockholms Universitet; Suecia
Fil: Mu, Xin. Stockholms Universitet; Suecia
Fil: Lang, Lisa. Stockholms Universitet; Suecia
Fil: Wang, Huabing. Stockholms Universitet; Suecia
Fil: Binolfi, Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Leibniz Institute of Molecular Pharmacology; Alemania
Fil: Theillet, François Xavier. Leibniz Institute of Molecular Pharmacology; Alemania
Fil: Bekei, Beata. Leibniz Institute of Molecular Pharmacology; Alemania
Fil: Logan, Derek T.. Lund University; Suecia
Fil: Selenko, Philipp. Leibniz Institute of Molecular Pharmacology; Alemania
Fil: Wennerström, Håkan. Lund University; Suecia
Fil: Oliveberg, Mikael. Stockholms Universitet; Suecia
Materia
CROWDING
IN VIVO
NMR
PROTEIN STABILITY
THERMODYNAMICS
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:11336/52589
Acceder
id CONICETDig_ca95983b7e279f28aed79504582c657d
oai_identifier_str oai:ri.conicet.gov.ar:11336/52589
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Thermodynamics of protein destabilization in live cellsDanielsson, JensMu, XinLang, LisaWang, HuabingBinolfi, AndrésTheillet, François XavierBekei, BeataLogan, Derek T.Selenko, PhilippWennerström, HåkanOliveberg, MikaelCROWDINGIN VIVONMRPROTEIN STABILITYTHERMODYNAMICShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Although protein folding and stability have been well explored under simplified conditions in vitro, it is yet unclear how these basic self-organization events are modulated by the crowded interior of live cells. To find out, we use here in-cell NMR to follow at atomic resolution the thermal unfolding of a ß-barrel protein inside mammalian and bacterial cells. Challenging the view from in vitro crowding effects, we find that the cells destabilize the protein at 37°C but with a conspicuous twist While the melting temperature goes down the cold unfolding moves into the physiological regime, coupled to an augmented heat-capacity change. The effect seems induced by transient, sequence-specific, interactions with the cellular components, acting preferentially on the unfolded ensemble. This points to a model where the in vivo influence on protein behavior is case specific, determined by the individual protein's interplay with the functionally optimized "interaction landscape" of the cellular interior.Fil: Danielsson, Jens. Stockholms Universitet; SueciaFil: Mu, Xin. Stockholms Universitet; SueciaFil: Lang, Lisa. Stockholms Universitet; SueciaFil: Wang, Huabing. Stockholms Universitet; SueciaFil: Binolfi, Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Leibniz Institute of Molecular Pharmacology; AlemaniaFil: Theillet, François Xavier. Leibniz Institute of Molecular Pharmacology; AlemaniaFil: Bekei, Beata. Leibniz Institute of Molecular Pharmacology; AlemaniaFil: Logan, Derek T.. Lund University; SueciaFil: Selenko, Philipp. Leibniz Institute of Molecular Pharmacology; AlemaniaFil: Wennerström, Håkan. Lund University; SueciaFil: Oliveberg, Mikael. Stockholms Universitet; SueciaNational Academy of Sciences2015-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/52589Danielsson, Jens; Mu, Xin; Lang, Lisa; Wang, Huabing; Binolfi, Andrés; et al.; Thermodynamics of protein destabilization in live cells; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 112; 40; 10-2015; 12402-124070027-8424CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.1511308112info:eu-repo/semantics/altIdentifier/url/http://www.pnas.org/content/112/40/12402info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-03-31T14:47:00Zoai:ri.conicet.gov.ar:11336/52589instacron: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:34982026-03-31 14:47:00.448CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Thermodynamics of protein destabilization in live cells
title Thermodynamics of protein destabilization in live cells
spellingShingle Thermodynamics of protein destabilization in live cells
Danielsson, Jens
CROWDING
IN VIVO
NMR
PROTEIN STABILITY
THERMODYNAMICS
title_short Thermodynamics of protein destabilization in live cells
title_full Thermodynamics of protein destabilization in live cells
title_fullStr Thermodynamics of protein destabilization in live cells
title_full_unstemmed Thermodynamics of protein destabilization in live cells
title_sort Thermodynamics of protein destabilization in live cells
dc.creator.none.fl_str_mv Danielsson, Jens
Mu, Xin
Lang, Lisa
Wang, Huabing
Binolfi, Andrés
Theillet, François Xavier
Bekei, Beata
Logan, Derek T.
Selenko, Philipp
Wennerström, Håkan
Oliveberg, Mikael
author Danielsson, Jens
author_facet Danielsson, Jens
Mu, Xin
Lang, Lisa
Wang, Huabing
Binolfi, Andrés
Theillet, François Xavier
Bekei, Beata
Logan, Derek T.
Selenko, Philipp
Wennerström, Håkan
Oliveberg, Mikael
author_role author
author2 Mu, Xin
Lang, Lisa
Wang, Huabing
Binolfi, Andrés
Theillet, François Xavier
Bekei, Beata
Logan, Derek T.
Selenko, Philipp
Wennerström, Håkan
Oliveberg, Mikael
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CROWDING
IN VIVO
NMR
PROTEIN STABILITY
THERMODYNAMICS
topic CROWDING
IN VIVO
NMR
PROTEIN STABILITY
THERMODYNAMICS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Although protein folding and stability have been well explored under simplified conditions in vitro, it is yet unclear how these basic self-organization events are modulated by the crowded interior of live cells. To find out, we use here in-cell NMR to follow at atomic resolution the thermal unfolding of a ß-barrel protein inside mammalian and bacterial cells. Challenging the view from in vitro crowding effects, we find that the cells destabilize the protein at 37°C but with a conspicuous twist While the melting temperature goes down the cold unfolding moves into the physiological regime, coupled to an augmented heat-capacity change. The effect seems induced by transient, sequence-specific, interactions with the cellular components, acting preferentially on the unfolded ensemble. This points to a model where the in vivo influence on protein behavior is case specific, determined by the individual protein's interplay with the functionally optimized "interaction landscape" of the cellular interior.
Fil: Danielsson, Jens. Stockholms Universitet; Suecia
Fil: Mu, Xin. Stockholms Universitet; Suecia
Fil: Lang, Lisa. Stockholms Universitet; Suecia
Fil: Wang, Huabing. Stockholms Universitet; Suecia
Fil: Binolfi, Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Leibniz Institute of Molecular Pharmacology; Alemania
Fil: Theillet, François Xavier. Leibniz Institute of Molecular Pharmacology; Alemania
Fil: Bekei, Beata. Leibniz Institute of Molecular Pharmacology; Alemania
Fil: Logan, Derek T.. Lund University; Suecia
Fil: Selenko, Philipp. Leibniz Institute of Molecular Pharmacology; Alemania
Fil: Wennerström, Håkan. Lund University; Suecia
Fil: Oliveberg, Mikael. Stockholms Universitet; Suecia
description Although protein folding and stability have been well explored under simplified conditions in vitro, it is yet unclear how these basic self-organization events are modulated by the crowded interior of live cells. To find out, we use here in-cell NMR to follow at atomic resolution the thermal unfolding of a ß-barrel protein inside mammalian and bacterial cells. Challenging the view from in vitro crowding effects, we find that the cells destabilize the protein at 37°C but with a conspicuous twist While the melting temperature goes down the cold unfolding moves into the physiological regime, coupled to an augmented heat-capacity change. The effect seems induced by transient, sequence-specific, interactions with the cellular components, acting preferentially on the unfolded ensemble. This points to a model where the in vivo influence on protein behavior is case specific, determined by the individual protein's interplay with the functionally optimized "interaction landscape" of the cellular interior.
publishDate 2015
dc.date.none.fl_str_mv 2015-10
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/11336/52589
Danielsson, Jens; Mu, Xin; Lang, Lisa; Wang, Huabing; Binolfi, Andrés; et al.; Thermodynamics of protein destabilization in live cells; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 112; 40; 10-2015; 12402-12407
0027-8424
CONICET Digital
CONICET
url http://hdl.handle.net/11336/52589
identifier_str_mv Danielsson, Jens; Mu, Xin; Lang, Lisa; Wang, Huabing; Binolfi, Andrés; et al.; Thermodynamics of protein destabilization in live cells; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 112; 40; 10-2015; 12402-12407
0027-8424
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.1511308112
info:eu-repo/semantics/altIdentifier/url/http://www.pnas.org/content/112/40/12402
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 National Academy of Sciences
publisher.none.fl_str_mv National Academy of Sciences
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_ 1861213869069828096
score 12.822162

Publicaciones similares