Allosteric coupling activation mechanism in histidine kinases

Autores
Almada, Juan Cruz; Bortolotti, Ana; Porrini, Lucía; Albanesi, Daniela; Miguel, Virginia; Cybulski, Larisa Estefania
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Histidine kinases (HKs) are crucial regulators of cellular functions, mediating the phosphorylation of specific proteins to modulate their activity and localization. Upon signal detection, HKs transfer a phosphate group from ATP to a conserved histidine residue within their Dimerization and Histidine phosphotransfer (DHp) domain, subsequently passing the phosphate to a response regulator (RR) that typically interacts with DNA promoters to regulate gene expression.This study investigates the signal transduction mechanism of Bacillus subtilis HK DesK. We conducted substitutions on the conserved phospho-acceptor histidine and evaluated their effects on DesK´s activity in both in vivo and in vitro contexts. Notably, we found that a variant of DesK lacking the conserved histidine could still activate gene expression. Furthermore, computational simulations of DesK variants complexed with DesR revealed interactions that could be required to maintain DesR´s active conformation.Our findings elucidate an alternative pathway for RR activation via an allosteric mechanism that operates independently of histidine phosphorylation. We also demonstrated that Escherichia coli HK EnvZ, when lacking the conserved histidine, can activate gene expression. This HK-Allosteric Coupling Activation Mechanism (HK-ACAM) functions without reliance on phosphorylation or ATP consumption, potentially serving as a fail-safe mechanism under nutrient-limited conditions.
Fil: Almada, Juan Cruz. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina
Fil: Bortolotti, Ana. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina
Fil: Porrini, Lucía. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina
Fil: Albanesi, Daniela. 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: Miguel, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina
Fil: Cybulski, Larisa Estefania. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina
Materia
HISTIDIN KINASE
BACTERIAL SIGNAL TRANSDUCTION
ALLOSTERIC REGULATION
PROTEIN PHOSPHORYLATION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/274523
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/274523
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Allosteric coupling activation mechanism in histidine kinasesAlmada, Juan CruzBortolotti, AnaPorrini, LucíaAlbanesi, DanielaMiguel, VirginiaCybulski, Larisa EstefaniaHISTIDIN KINASEBACTERIAL SIGNAL TRANSDUCTIONALLOSTERIC REGULATIONPROTEIN PHOSPHORYLATIONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Histidine kinases (HKs) are crucial regulators of cellular functions, mediating the phosphorylation of specific proteins to modulate their activity and localization. Upon signal detection, HKs transfer a phosphate group from ATP to a conserved histidine residue within their Dimerization and Histidine phosphotransfer (DHp) domain, subsequently passing the phosphate to a response regulator (RR) that typically interacts with DNA promoters to regulate gene expression.This study investigates the signal transduction mechanism of Bacillus subtilis HK DesK. We conducted substitutions on the conserved phospho-acceptor histidine and evaluated their effects on DesK´s activity in both in vivo and in vitro contexts. Notably, we found that a variant of DesK lacking the conserved histidine could still activate gene expression. Furthermore, computational simulations of DesK variants complexed with DesR revealed interactions that could be required to maintain DesR´s active conformation.Our findings elucidate an alternative pathway for RR activation via an allosteric mechanism that operates independently of histidine phosphorylation. We also demonstrated that Escherichia coli HK EnvZ, when lacking the conserved histidine, can activate gene expression. This HK-Allosteric Coupling Activation Mechanism (HK-ACAM) functions without reliance on phosphorylation or ATP consumption, potentially serving as a fail-safe mechanism under nutrient-limited conditions.Fil: Almada, Juan Cruz. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaFil: Bortolotti, Ana. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaFil: Porrini, Lucía. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaFil: Albanesi, Daniela. 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: Miguel, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; ArgentinaFil: Cybulski, Larisa Estefania. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaSpringer2025-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/274523Almada, Juan Cruz; Bortolotti, Ana; Porrini, Lucía; Albanesi, Daniela; Miguel, Virginia; et al.; Allosteric coupling activation mechanism in histidine kinases; Springer; Scientific Reports; 15; 1; 4-2025; 1-132045-2322CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-025-88468-5info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-11-05T10:03:35Zoai:ri.conicet.gov.ar:11336/274523instacron: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:34982025-11-05 10:03:35.376CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Allosteric coupling activation mechanism in histidine kinases
title Allosteric coupling activation mechanism in histidine kinases
spellingShingle Allosteric coupling activation mechanism in histidine kinases
Almada, Juan Cruz
HISTIDIN KINASE
BACTERIAL SIGNAL TRANSDUCTION
ALLOSTERIC REGULATION
PROTEIN PHOSPHORYLATION
title_short Allosteric coupling activation mechanism in histidine kinases
title_full Allosteric coupling activation mechanism in histidine kinases
title_fullStr Allosteric coupling activation mechanism in histidine kinases
title_full_unstemmed Allosteric coupling activation mechanism in histidine kinases
title_sort Allosteric coupling activation mechanism in histidine kinases
dc.creator.none.fl_str_mv Almada, Juan Cruz
Bortolotti, Ana
Porrini, Lucía
Albanesi, Daniela
Miguel, Virginia
Cybulski, Larisa Estefania
author Almada, Juan Cruz
author_facet Almada, Juan Cruz
Bortolotti, Ana
Porrini, Lucía
Albanesi, Daniela
Miguel, Virginia
Cybulski, Larisa Estefania
author_role author
author2 Bortolotti, Ana
Porrini, Lucía
Albanesi, Daniela
Miguel, Virginia
Cybulski, Larisa Estefania
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv HISTIDIN KINASE
BACTERIAL SIGNAL TRANSDUCTION
ALLOSTERIC REGULATION
PROTEIN PHOSPHORYLATION
topic HISTIDIN KINASE
BACTERIAL SIGNAL TRANSDUCTION
ALLOSTERIC REGULATION
PROTEIN PHOSPHORYLATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Histidine kinases (HKs) are crucial regulators of cellular functions, mediating the phosphorylation of specific proteins to modulate their activity and localization. Upon signal detection, HKs transfer a phosphate group from ATP to a conserved histidine residue within their Dimerization and Histidine phosphotransfer (DHp) domain, subsequently passing the phosphate to a response regulator (RR) that typically interacts with DNA promoters to regulate gene expression.This study investigates the signal transduction mechanism of Bacillus subtilis HK DesK. We conducted substitutions on the conserved phospho-acceptor histidine and evaluated their effects on DesK´s activity in both in vivo and in vitro contexts. Notably, we found that a variant of DesK lacking the conserved histidine could still activate gene expression. Furthermore, computational simulations of DesK variants complexed with DesR revealed interactions that could be required to maintain DesR´s active conformation.Our findings elucidate an alternative pathway for RR activation via an allosteric mechanism that operates independently of histidine phosphorylation. We also demonstrated that Escherichia coli HK EnvZ, when lacking the conserved histidine, can activate gene expression. This HK-Allosteric Coupling Activation Mechanism (HK-ACAM) functions without reliance on phosphorylation or ATP consumption, potentially serving as a fail-safe mechanism under nutrient-limited conditions.
Fil: Almada, Juan Cruz. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina
Fil: Bortolotti, Ana. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina
Fil: Porrini, Lucía. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina
Fil: Albanesi, Daniela. 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: Miguel, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina
Fil: Cybulski, Larisa Estefania. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina
description Histidine kinases (HKs) are crucial regulators of cellular functions, mediating the phosphorylation of specific proteins to modulate their activity and localization. Upon signal detection, HKs transfer a phosphate group from ATP to a conserved histidine residue within their Dimerization and Histidine phosphotransfer (DHp) domain, subsequently passing the phosphate to a response regulator (RR) that typically interacts with DNA promoters to regulate gene expression.This study investigates the signal transduction mechanism of Bacillus subtilis HK DesK. We conducted substitutions on the conserved phospho-acceptor histidine and evaluated their effects on DesK´s activity in both in vivo and in vitro contexts. Notably, we found that a variant of DesK lacking the conserved histidine could still activate gene expression. Furthermore, computational simulations of DesK variants complexed with DesR revealed interactions that could be required to maintain DesR´s active conformation.Our findings elucidate an alternative pathway for RR activation via an allosteric mechanism that operates independently of histidine phosphorylation. We also demonstrated that Escherichia coli HK EnvZ, when lacking the conserved histidine, can activate gene expression. This HK-Allosteric Coupling Activation Mechanism (HK-ACAM) functions without reliance on phosphorylation or ATP consumption, potentially serving as a fail-safe mechanism under nutrient-limited conditions.
publishDate 2025
dc.date.none.fl_str_mv 2025-04
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/11336/274523
Almada, Juan Cruz; Bortolotti, Ana; Porrini, Lucía; Albanesi, Daniela; Miguel, Virginia; et al.; Allosteric coupling activation mechanism in histidine kinases; Springer; Scientific Reports; 15; 1; 4-2025; 1-13
2045-2322
CONICET Digital
CONICET
url http://hdl.handle.net/11336/274523
identifier_str_mv Almada, Juan Cruz; Bortolotti, Ana; Porrini, Lucía; Albanesi, Daniela; Miguel, Virginia; et al.; Allosteric coupling activation mechanism in histidine kinases; Springer; Scientific Reports; 15; 1; 4-2025; 1-13
2045-2322
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-025-88468-5
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
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 13.084122

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