Activation of the bacterial thermosensor DesK involves a serine zipper dimerization motif that is modulated by bilayer thickness

Autores
Cybulski, Larisa Estefania; Ballering, Joost; Moussatova, Anastassiia; Inda, María Eugenia; Vázquez, Daniela Belén; Wassenaar, Tsjerk A.; de Mendoza, Diego; Tieleman, D. Peter; Killian, J. Antoinette
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
DesK is a bacterial thermosensor protein involved in maintaining membrane fluidity in response to changes in environmental temperature. Most likely, the protein is activated by changes in membrane thickness, but the molecular mechanism of sensing and signaling is still poorly understood. Here we aimed to elucidate the mode of action of DesK by studying the so-called "minimal sensor DesK" (MS-DesK), in which sensing and signaling are captured in a single transmembrane segment. This simplified version of the sensor allows investigation of membrane thickness-dependent protein-lipid interactions simply by using synthetic peptides, corresponding to the membrane-spanning parts of functional and nonfunctional mutants of MS-DesK incorporated in lipid bilayers with varying thicknesses. The lipid-dependent behavior of the peptides was investigated by circular dichroism, tryptophan fluorescence, and molecular modeling. These experiments were complemented with in vivo functional studies on MS-DesK mutants. Based on the results, we constructed a model that suggests a new mechanism for sensing in which the protein is present as a dimer and responds to an increase in bilayer thickness by membrane incorporation of a C-terminal hydrophilic motif. This results in exposure of three serines on the same side of the transmembrane helices of MS-DesK, triggering a switching of the dimerization interface to allow the formation of a serine zipper. The final result is activation of the kinase state of MS-DesK.
Fil: Cybulski, Larisa Estefania. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmaceuticas. Departamento de Microbiología; Argentina
Fil: Ballering, Joost. University of Utrecht; Países Bajos
Fil: Moussatova, Anastassiia. University of Calgary,; Canadá
Fil: Inda, María Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmaceuticas. Departamento de Microbiología; Argentina
Fil: Vázquez, Daniela Belén. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmaceuticas. Departamento de Microbiología; Argentina
Fil: Wassenaar, Tsjerk A.. University of Erlangen-Nürnberg; Alemania
Fil: de Mendoza, Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Tieleman, D. Peter. University of Calgary,; Canadá
Fil: Killian, J. Antoinette. University of Utrecht; Países Bajos
Materia
HELIX-HELIX INTERACTION|
LIPID-PROTEIN INTERACTION|
THERMOSENSING|
TRANSMEMBRANE HELIX DIMERIZATION
TWO-COMPONENT SYSTEM|
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:11336/49914
Acceder
id CONICETDig_04af2fc66f215627637e6d1aa4678a8e
oai_identifier_str oai:ri.conicet.gov.ar:11336/49914
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Activation of the bacterial thermosensor DesK involves a serine zipper dimerization motif that is modulated by bilayer thicknessCybulski, Larisa EstefaniaBallering, JoostMoussatova, AnastassiiaInda, María EugeniaVázquez, Daniela BelénWassenaar, Tsjerk A.de Mendoza, DiegoTieleman, D. PeterKillian, J. AntoinetteHELIX-HELIX INTERACTION|LIPID-PROTEIN INTERACTION|THERMOSENSING|TRANSMEMBRANE HELIX DIMERIZATIONTWO-COMPONENT SYSTEM|https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1DesK is a bacterial thermosensor protein involved in maintaining membrane fluidity in response to changes in environmental temperature. Most likely, the protein is activated by changes in membrane thickness, but the molecular mechanism of sensing and signaling is still poorly understood. Here we aimed to elucidate the mode of action of DesK by studying the so-called "minimal sensor DesK" (MS-DesK), in which sensing and signaling are captured in a single transmembrane segment. This simplified version of the sensor allows investigation of membrane thickness-dependent protein-lipid interactions simply by using synthetic peptides, corresponding to the membrane-spanning parts of functional and nonfunctional mutants of MS-DesK incorporated in lipid bilayers with varying thicknesses. The lipid-dependent behavior of the peptides was investigated by circular dichroism, tryptophan fluorescence, and molecular modeling. These experiments were complemented with in vivo functional studies on MS-DesK mutants. Based on the results, we constructed a model that suggests a new mechanism for sensing in which the protein is present as a dimer and responds to an increase in bilayer thickness by membrane incorporation of a C-terminal hydrophilic motif. This results in exposure of three serines on the same side of the transmembrane helices of MS-DesK, triggering a switching of the dimerization interface to allow the formation of a serine zipper. The final result is activation of the kinase state of MS-DesK.Fil: Cybulski, Larisa Estefania. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmaceuticas. Departamento de Microbiología; ArgentinaFil: Ballering, Joost. University of Utrecht; Países BajosFil: Moussatova, Anastassiia. University of Calgary,; CanadáFil: Inda, María Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmaceuticas. Departamento de Microbiología; ArgentinaFil: Vázquez, Daniela Belén. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmaceuticas. Departamento de Microbiología; ArgentinaFil: Wassenaar, Tsjerk A.. University of Erlangen-Nürnberg; AlemaniaFil: de Mendoza, Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Tieleman, D. Peter. University of Calgary,; CanadáFil: Killian, J. Antoinette. University of Utrecht; Países BajosNational Academy of Sciences2015-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/49914Cybulski, Larisa Estefania; Ballering, Joost; Moussatova, Anastassiia; Inda, María Eugenia; Vázquez, Daniela Belén; et al.; Activation of the bacterial thermosensor DesK involves a serine zipper dimerization motif that is modulated by bilayer thickness; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 112; 20; 5-2015; 6353-63580027-8424CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.1422446112info:eu-repo/semantics/altIdentifier/url/http://www.pnas.org/content/112/20/6353info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:33:51Zoai:ri.conicet.gov.ar:11336/49914instacron: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:34982025-10-15 15:33:51.733CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Activation of the bacterial thermosensor DesK involves a serine zipper dimerization motif that is modulated by bilayer thickness
title Activation of the bacterial thermosensor DesK involves a serine zipper dimerization motif that is modulated by bilayer thickness
spellingShingle Activation of the bacterial thermosensor DesK involves a serine zipper dimerization motif that is modulated by bilayer thickness
Cybulski, Larisa Estefania
HELIX-HELIX INTERACTION|
LIPID-PROTEIN INTERACTION|
THERMOSENSING|
TRANSMEMBRANE HELIX DIMERIZATION
TWO-COMPONENT SYSTEM|
title_short Activation of the bacterial thermosensor DesK involves a serine zipper dimerization motif that is modulated by bilayer thickness
title_full Activation of the bacterial thermosensor DesK involves a serine zipper dimerization motif that is modulated by bilayer thickness
title_fullStr Activation of the bacterial thermosensor DesK involves a serine zipper dimerization motif that is modulated by bilayer thickness
title_full_unstemmed Activation of the bacterial thermosensor DesK involves a serine zipper dimerization motif that is modulated by bilayer thickness
title_sort Activation of the bacterial thermosensor DesK involves a serine zipper dimerization motif that is modulated by bilayer thickness
dc.creator.none.fl_str_mv Cybulski, Larisa Estefania
Ballering, Joost
Moussatova, Anastassiia
Inda, María Eugenia
Vázquez, Daniela Belén
Wassenaar, Tsjerk A.
de Mendoza, Diego
Tieleman, D. Peter
Killian, J. Antoinette
author Cybulski, Larisa Estefania
author_facet Cybulski, Larisa Estefania
Ballering, Joost
Moussatova, Anastassiia
Inda, María Eugenia
Vázquez, Daniela Belén
Wassenaar, Tsjerk A.
de Mendoza, Diego
Tieleman, D. Peter
Killian, J. Antoinette
author_role author
author2 Ballering, Joost
Moussatova, Anastassiia
Inda, María Eugenia
Vázquez, Daniela Belén
Wassenaar, Tsjerk A.
de Mendoza, Diego
Tieleman, D. Peter
Killian, J. Antoinette
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv HELIX-HELIX INTERACTION|
LIPID-PROTEIN INTERACTION|
THERMOSENSING|
TRANSMEMBRANE HELIX DIMERIZATION
TWO-COMPONENT SYSTEM|
topic HELIX-HELIX INTERACTION|
LIPID-PROTEIN INTERACTION|
THERMOSENSING|
TRANSMEMBRANE HELIX DIMERIZATION
TWO-COMPONENT SYSTEM|
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv DesK is a bacterial thermosensor protein involved in maintaining membrane fluidity in response to changes in environmental temperature. Most likely, the protein is activated by changes in membrane thickness, but the molecular mechanism of sensing and signaling is still poorly understood. Here we aimed to elucidate the mode of action of DesK by studying the so-called "minimal sensor DesK" (MS-DesK), in which sensing and signaling are captured in a single transmembrane segment. This simplified version of the sensor allows investigation of membrane thickness-dependent protein-lipid interactions simply by using synthetic peptides, corresponding to the membrane-spanning parts of functional and nonfunctional mutants of MS-DesK incorporated in lipid bilayers with varying thicknesses. The lipid-dependent behavior of the peptides was investigated by circular dichroism, tryptophan fluorescence, and molecular modeling. These experiments were complemented with in vivo functional studies on MS-DesK mutants. Based on the results, we constructed a model that suggests a new mechanism for sensing in which the protein is present as a dimer and responds to an increase in bilayer thickness by membrane incorporation of a C-terminal hydrophilic motif. This results in exposure of three serines on the same side of the transmembrane helices of MS-DesK, triggering a switching of the dimerization interface to allow the formation of a serine zipper. The final result is activation of the kinase state of MS-DesK.
Fil: Cybulski, Larisa Estefania. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmaceuticas. Departamento de Microbiología; Argentina
Fil: Ballering, Joost. University of Utrecht; Países Bajos
Fil: Moussatova, Anastassiia. University of Calgary,; Canadá
Fil: Inda, María Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmaceuticas. Departamento de Microbiología; Argentina
Fil: Vázquez, Daniela Belén. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmaceuticas. Departamento de Microbiología; Argentina
Fil: Wassenaar, Tsjerk A.. University of Erlangen-Nürnberg; Alemania
Fil: de Mendoza, Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Tieleman, D. Peter. University of Calgary,; Canadá
Fil: Killian, J. Antoinette. University of Utrecht; Países Bajos
description DesK is a bacterial thermosensor protein involved in maintaining membrane fluidity in response to changes in environmental temperature. Most likely, the protein is activated by changes in membrane thickness, but the molecular mechanism of sensing and signaling is still poorly understood. Here we aimed to elucidate the mode of action of DesK by studying the so-called "minimal sensor DesK" (MS-DesK), in which sensing and signaling are captured in a single transmembrane segment. This simplified version of the sensor allows investigation of membrane thickness-dependent protein-lipid interactions simply by using synthetic peptides, corresponding to the membrane-spanning parts of functional and nonfunctional mutants of MS-DesK incorporated in lipid bilayers with varying thicknesses. The lipid-dependent behavior of the peptides was investigated by circular dichroism, tryptophan fluorescence, and molecular modeling. These experiments were complemented with in vivo functional studies on MS-DesK mutants. Based on the results, we constructed a model that suggests a new mechanism for sensing in which the protein is present as a dimer and responds to an increase in bilayer thickness by membrane incorporation of a C-terminal hydrophilic motif. This results in exposure of three serines on the same side of the transmembrane helices of MS-DesK, triggering a switching of the dimerization interface to allow the formation of a serine zipper. The final result is activation of the kinase state of MS-DesK.
publishDate 2015
dc.date.none.fl_str_mv 2015-05
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/11336/49914
Cybulski, Larisa Estefania; Ballering, Joost; Moussatova, Anastassiia; Inda, María Eugenia; Vázquez, Daniela Belén; et al.; Activation of the bacterial thermosensor DesK involves a serine zipper dimerization motif that is modulated by bilayer thickness; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 112; 20; 5-2015; 6353-6358
0027-8424
CONICET Digital
CONICET
url http://hdl.handle.net/11336/49914
identifier_str_mv Cybulski, Larisa Estefania; Ballering, Joost; Moussatova, Anastassiia; Inda, María Eugenia; Vázquez, Daniela Belén; et al.; Activation of the bacterial thermosensor DesK involves a serine zipper dimerization motif that is modulated by bilayer thickness; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 112; 20; 5-2015; 6353-6358
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.1422446112
info:eu-repo/semantics/altIdentifier/url/http://www.pnas.org/content/112/20/6353
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
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
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score 13.22299

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