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Allosteric coupling activation mechanism in histidine kinases
by
Albanesi, Daniela
, Cybulski, Larisa
, Bortolotti, Ana
, Porrini, Lucía
, Almada, Juan Cruz
, Miguel, Virginia
in
631/45/275
/ 631/45/612/1237
/ 631/45/612/1246
/ Allosteric Regulation
/ Bacillus subtilis - enzymology
/ Bacillus subtilis - genetics
/ Bacillus subtilis - metabolism
/ Bacterial Outer Membrane Proteins
/ Bacterial Proteins - chemistry
/ Bacterial Proteins - genetics
/ Bacterial Proteins - metabolism
/ Bacterial signal transduction
/ Escherichia coli - genetics
/ Escherichia coli - metabolism
/ Escherichia coli Proteins - chemistry
/ Escherichia coli Proteins - genetics
/ Escherichia coli Proteins - metabolism
/ Gene Expression Regulation, Bacterial
/ Histidine - metabolism
/ Histidine kinase
/ Histidine Kinase - chemistry
/ Histidine Kinase - genetics
/ Histidine Kinase - metabolism
/ Humanities and Social Sciences
/ multidisciplinary
/ Multienzyme Complexes
/ Phosphorylation
/ Protein phosphorylation
/ Protein–protein interaction
/ Science
/ Science (multidisciplinary)
/ Signal Transduction
/ Two-component system
2025
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Allosteric coupling activation mechanism in histidine kinases
by
Albanesi, Daniela
, Cybulski, Larisa
, Bortolotti, Ana
, Porrini, Lucía
, Almada, Juan Cruz
, Miguel, Virginia
in
631/45/275
/ 631/45/612/1237
/ 631/45/612/1246
/ Allosteric Regulation
/ Bacillus subtilis - enzymology
/ Bacillus subtilis - genetics
/ Bacillus subtilis - metabolism
/ Bacterial Outer Membrane Proteins
/ Bacterial Proteins - chemistry
/ Bacterial Proteins - genetics
/ Bacterial Proteins - metabolism
/ Bacterial signal transduction
/ Escherichia coli - genetics
/ Escherichia coli - metabolism
/ Escherichia coli Proteins - chemistry
/ Escherichia coli Proteins - genetics
/ Escherichia coli Proteins - metabolism
/ Gene Expression Regulation, Bacterial
/ Histidine - metabolism
/ Histidine kinase
/ Histidine Kinase - chemistry
/ Histidine Kinase - genetics
/ Histidine Kinase - metabolism
/ Humanities and Social Sciences
/ multidisciplinary
/ Multienzyme Complexes
/ Phosphorylation
/ Protein phosphorylation
/ Protein–protein interaction
/ Science
/ Science (multidisciplinary)
/ Signal Transduction
/ Two-component system
2025
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Allosteric coupling activation mechanism in histidine kinases
by
Albanesi, Daniela
, Cybulski, Larisa
, Bortolotti, Ana
, Porrini, Lucía
, Almada, Juan Cruz
, Miguel, Virginia
in
631/45/275
/ 631/45/612/1237
/ 631/45/612/1246
/ Allosteric Regulation
/ Bacillus subtilis - enzymology
/ Bacillus subtilis - genetics
/ Bacillus subtilis - metabolism
/ Bacterial Outer Membrane Proteins
/ Bacterial Proteins - chemistry
/ Bacterial Proteins - genetics
/ Bacterial Proteins - metabolism
/ Bacterial signal transduction
/ Escherichia coli - genetics
/ Escherichia coli - metabolism
/ Escherichia coli Proteins - chemistry
/ Escherichia coli Proteins - genetics
/ Escherichia coli Proteins - metabolism
/ Gene Expression Regulation, Bacterial
/ Histidine - metabolism
/ Histidine kinase
/ Histidine Kinase - chemistry
/ Histidine Kinase - genetics
/ Histidine Kinase - metabolism
/ Humanities and Social Sciences
/ multidisciplinary
/ Multienzyme Complexes
/ Phosphorylation
/ Protein phosphorylation
/ Protein–protein interaction
/ Science
/ Science (multidisciplinary)
/ Signal Transduction
/ Two-component system
2025
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Allosteric coupling activation mechanism in histidine kinases
Journal Article
Allosteric coupling activation mechanism in histidine kinases
2025
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Overview
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 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 generated 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 functions without reliance on phosphorylation or ATP consumption, potentially serving as a fail-safe mechanism under nutrient-limited conditions.
Publisher
Nature Publishing Group UK,Nature Portfolio
Subject
/ Bacillus subtilis - enzymology
/ Bacillus subtilis - genetics
/ Bacillus subtilis - metabolism
/ Bacterial Outer Membrane Proteins
/ Bacterial Proteins - chemistry
/ Bacterial Proteins - genetics
/ Bacterial Proteins - metabolism
/ Bacterial signal transduction
/ Escherichia coli - metabolism
/ Escherichia coli Proteins - chemistry
/ Escherichia coli Proteins - genetics
/ Escherichia coli Proteins - metabolism
/ Gene Expression Regulation, Bacterial
/ Histidine Kinase - chemistry
/ Histidine Kinase - metabolism
/ Humanities and Social Sciences
/ Science
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