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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/7607
Ver los metadatos del registro completo
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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 Técnicas2025-09-29T09:52:36Zoai: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:34982025-09-29 09:52:36.542CONICET 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 |
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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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13.070432 |