A lipid-mediated conformational switch modulates the thermosensing activity of DesK

Autores
Inda, María Eugenia; Vandenbranden, Michel; Fernandez, Ariel; de Mendoza, Diego; Ruysschaert, Jean Marie; Cybulski, Larisa Estefania
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The thermosensor DesK is a multipass transmembrane histidine-kinase that allows the bacterium Bacillus subtilis to adjust the levels of unsaturated fatty acids required to optimize membrane lipid fluidity. The cytoplasmic catalytic domain of DesK behaves like a kinase at low temperature and like a phosphatase at high temperature. Temperature sensing involves a built-in instability caused by a group of hydrophilic residues located near the N terminus of the first transmembrane (TM) segment. These residues are buried in the lipid phase at low temperature and partially “buoy” to the aqueous phase at higher temperature with the thinning of the membrane, promoting the required conformational change. Nevertheless, the core question remains poorly understood: How is the information sensed by the transmembrane region converted into a rearrangement in the cytoplasmic catalytic domain to control DesK activity? Here, we identify a “linker region” (KSRKERERLEEK) that connects the TM sensor domain with the cytoplasmic catalytic domain involved in signal transmission. The linker adopts two conformational states in response to temperature-dependent membrane thickness changes: (i) random coiled and bound to the phospholipid head groups at the water-membrane interface, promoting the phosphatase state or (ii) unbound and forming a continuous helix spanning a region from the membrane to the cytoplasm, promoting the kinase state. Our results uphold the view that the linker is endowed with a helix/random coil conformational duality that enables it to behave like a transmission switch, with helix disruption decreasing the kinase/phosphatase activity ratio, as required to modulate the DesK output response.
Fil: Inda, María Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Vandenbranden, Michel. Universite Libre de Bruxelles; Bélgica
Fil: Fernandez, Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Instituto Argentino de Matemática; Argentina. Collegium Basilea. Institute of Advanced Study; Suiza
Fil: de Mendoza, Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Ruysschaert, Jean Marie. Universite Libre de Bruxelles; Bélgica
Fil: Cybulski, Larisa Estefania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Biología Molecular y Celular de Rosario; Argentina
Materia
Signal Transduction
Transmembrane Sensor
Conformational Switch
Kinase
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:11336/7607
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/7607
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling A lipid-mediated conformational switch modulates the thermosensing activity of DesKInda, María EugeniaVandenbranden, MichelFernandez, Arielde Mendoza, DiegoRuysschaert, Jean MarieCybulski, Larisa EstefaniaSignal TransductionTransmembrane SensorConformational SwitchKinasehttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The thermosensor DesK is a multipass transmembrane histidine-kinase that allows the bacterium Bacillus subtilis to adjust the levels of unsaturated fatty acids required to optimize membrane lipid fluidity. The cytoplasmic catalytic domain of DesK behaves like a kinase at low temperature and like a phosphatase at high temperature. Temperature sensing involves a built-in instability caused by a group of hydrophilic residues located near the N terminus of the first transmembrane (TM) segment. These residues are buried in the lipid phase at low temperature and partially “buoy” to the aqueous phase at higher temperature with the thinning of the membrane, promoting the required conformational change. Nevertheless, the core question remains poorly understood: How is the information sensed by the transmembrane region converted into a rearrangement in the cytoplasmic catalytic domain to control DesK activity? Here, we identify a “linker region” (KSRKERERLEEK) that connects the TM sensor domain with the cytoplasmic catalytic domain involved in signal transmission. The linker adopts two conformational states in response to temperature-dependent membrane thickness changes: (i) random coiled and bound to the phospholipid head groups at the water-membrane interface, promoting the phosphatase state or (ii) unbound and forming a continuous helix spanning a region from the membrane to the cytoplasm, promoting the kinase state. Our results uphold the view that the linker is endowed with a helix/random coil conformational duality that enables it to behave like a transmission switch, with helix disruption decreasing the kinase/phosphatase activity ratio, as required to modulate the DesK output response.Fil: Inda, María Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Vandenbranden, Michel. Universite Libre de Bruxelles; BélgicaFil: Fernandez, Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Instituto Argentino de Matemática; Argentina. Collegium Basilea. Institute of Advanced Study; SuizaFil: de Mendoza, Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Ruysschaert, Jean Marie. Universite Libre de Bruxelles; BélgicaFil: Cybulski, Larisa Estefania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Biología Molecular y Celular de Rosario; ArgentinaNational Academy Of Sciences2014-02info: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/11336/7607Inda, María Eugenia; Vandenbranden, Michel; Fernandez, Ariel; de Mendoza, Diego; Ruysschaert, Jean Marie; et al.; A lipid-mediated conformational switch modulates the thermosensing activity of DesK; National Academy Of Sciences; Proceedings Of The National Academy Of Sciences Of The United States Of America; 111; 9; 2-2014; 3579-35840027-8424enginfo:eu-repo/semantics/altIdentifier/url/http://www.pnas.org/content/111/9/3579info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.1317147111info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:22:00Zoai:ri.conicet.gov.ar:11336/7607instacron: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:34982025-10-22 11:22:00.303CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv A lipid-mediated conformational switch modulates the thermosensing activity of DesK
title A lipid-mediated conformational switch modulates the thermosensing activity of DesK
spellingShingle A lipid-mediated conformational switch modulates the thermosensing activity of DesK
Inda, María Eugenia
Signal Transduction
Transmembrane Sensor
Conformational Switch
Kinase
title_short A lipid-mediated conformational switch modulates the thermosensing activity of DesK
title_full A lipid-mediated conformational switch modulates the thermosensing activity of DesK
title_fullStr A lipid-mediated conformational switch modulates the thermosensing activity of DesK
title_full_unstemmed A lipid-mediated conformational switch modulates the thermosensing activity of DesK
title_sort A lipid-mediated conformational switch modulates the thermosensing activity of DesK
dc.creator.none.fl_str_mv Inda, María Eugenia
Vandenbranden, Michel
Fernandez, Ariel
de Mendoza, Diego
Ruysschaert, Jean Marie
Cybulski, Larisa Estefania
author Inda, María Eugenia
author_facet Inda, María Eugenia
Vandenbranden, Michel
Fernandez, Ariel
de Mendoza, Diego
Ruysschaert, Jean Marie
Cybulski, Larisa Estefania
author_role author
author2 Vandenbranden, Michel
Fernandez, Ariel
de Mendoza, Diego
Ruysschaert, Jean Marie
Cybulski, Larisa Estefania
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Signal Transduction
Transmembrane Sensor
Conformational Switch
Kinase
topic Signal Transduction
Transmembrane Sensor
Conformational Switch
Kinase
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 thermosensor DesK is a multipass transmembrane histidine-kinase that allows the bacterium Bacillus subtilis to adjust the levels of unsaturated fatty acids required to optimize membrane lipid fluidity. The cytoplasmic catalytic domain of DesK behaves like a kinase at low temperature and like a phosphatase at high temperature. Temperature sensing involves a built-in instability caused by a group of hydrophilic residues located near the N terminus of the first transmembrane (TM) segment. These residues are buried in the lipid phase at low temperature and partially “buoy” to the aqueous phase at higher temperature with the thinning of the membrane, promoting the required conformational change. Nevertheless, the core question remains poorly understood: How is the information sensed by the transmembrane region converted into a rearrangement in the cytoplasmic catalytic domain to control DesK activity? Here, we identify a “linker region” (KSRKERERLEEK) that connects the TM sensor domain with the cytoplasmic catalytic domain involved in signal transmission. The linker adopts two conformational states in response to temperature-dependent membrane thickness changes: (i) random coiled and bound to the phospholipid head groups at the water-membrane interface, promoting the phosphatase state or (ii) unbound and forming a continuous helix spanning a region from the membrane to the cytoplasm, promoting the kinase state. Our results uphold the view that the linker is endowed with a helix/random coil conformational duality that enables it to behave like a transmission switch, with helix disruption decreasing the kinase/phosphatase activity ratio, as required to modulate the DesK output response.
Fil: Inda, María Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Vandenbranden, Michel. Universite Libre de Bruxelles; Bélgica
Fil: Fernandez, Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Instituto Argentino de Matemática; Argentina. Collegium Basilea. Institute of Advanced Study; Suiza
Fil: de Mendoza, Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Ruysschaert, Jean Marie. Universite Libre de Bruxelles; Bélgica
Fil: Cybulski, Larisa Estefania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Biología Molecular y Celular de Rosario; Argentina
description The thermosensor DesK is a multipass transmembrane histidine-kinase that allows the bacterium Bacillus subtilis to adjust the levels of unsaturated fatty acids required to optimize membrane lipid fluidity. The cytoplasmic catalytic domain of DesK behaves like a kinase at low temperature and like a phosphatase at high temperature. Temperature sensing involves a built-in instability caused by a group of hydrophilic residues located near the N terminus of the first transmembrane (TM) segment. These residues are buried in the lipid phase at low temperature and partially “buoy” to the aqueous phase at higher temperature with the thinning of the membrane, promoting the required conformational change. Nevertheless, the core question remains poorly understood: How is the information sensed by the transmembrane region converted into a rearrangement in the cytoplasmic catalytic domain to control DesK activity? Here, we identify a “linker region” (KSRKERERLEEK) that connects the TM sensor domain with the cytoplasmic catalytic domain involved in signal transmission. The linker adopts two conformational states in response to temperature-dependent membrane thickness changes: (i) random coiled and bound to the phospholipid head groups at the water-membrane interface, promoting the phosphatase state or (ii) unbound and forming a continuous helix spanning a region from the membrane to the cytoplasm, promoting the kinase state. Our results uphold the view that the linker is endowed with a helix/random coil conformational duality that enables it to behave like a transmission switch, with helix disruption decreasing the kinase/phosphatase activity ratio, as required to modulate the DesK output response.
publishDate 2014
dc.date.none.fl_str_mv 2014-02
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/11336/7607
Inda, María Eugenia; Vandenbranden, Michel; Fernandez, Ariel; de Mendoza, Diego; Ruysschaert, Jean Marie; et al.; A lipid-mediated conformational switch modulates the thermosensing activity of DesK; National Academy Of Sciences; Proceedings Of The National Academy Of Sciences Of The United States Of America; 111; 9; 2-2014; 3579-3584
0027-8424
url http://hdl.handle.net/11336/7607
identifier_str_mv Inda, María Eugenia; Vandenbranden, Michel; Fernandez, Ariel; de Mendoza, Diego; Ruysschaert, Jean Marie; et al.; A lipid-mediated conformational switch modulates the thermosensing activity of DesK; National Academy Of Sciences; Proceedings Of The National Academy Of Sciences Of The United States Of America; 111; 9; 2-2014; 3579-3584
0027-8424
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.pnas.org/content/111/9/3579
info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.1317147111
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 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 12.982451

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